Startseite Analysis of some pharmaceuticals in the presence of their synthetic impurities by applying hybrid micelle liquid chromatography
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Analysis of some pharmaceuticals in the presence of their synthetic impurities by applying hybrid micelle liquid chromatography

  • Dina El Sherbiny und Mary E. K. Wahba EMAIL logo
Veröffentlicht/Copyright: 23. Mai 2020
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Open Chemistry
Aus der Zeitschrift Open Chemistry Band 18 Heft 1

Abstract

A stability-indicating hybrid micelle liquid chromatography accompanied by UV detection was developed for the simultaneous analysis of either paracetamol (PCA) or pseudoephedrine hydrochloride (PSU) with their synthetic impurities. Mixture I contains PCA with p-amino phenol and p-nitro phenol, while mixture II involves the estimation of PSU with benzaldehyde and benzoic acid. Both mixtures were separated using a C18 column that was thermostatically maintained at 40°C and operating under a flow rate of 1.5 mL/min, applying UV detection at 240 nm for mixture I and 220 nm for mixture II. In both cases, the mobile phase consisted of 0.1 M sodium dodecyl sulfate, acetonitrile, and triethylamine (90:10:0.3, v/v/v) and adjusted to pH 4 (mixture I) or pH 3.7 (mixture II) using 2.0 M O-phosphoric acid. The proposed method was validated and successfully applied to assay different pharmaceuticals containing PCA or PSU. Moreover, the stability-indicating nature of the proposed method was proved through applying photolytic degradation procedures for PCA.

Keywords: paracetamol; pseudoephedrine; impurities; degradation; micellar

1 Introduction

Potency and safety of pharmaceutical compounds are two major concerns during remedial treatment. Safety of any drug is judged by both its pharmacological–toxicological profile and the undesirable side effects which are in the vast majority, resulting from the impurities encountered in pharmaceutical formulations [1]. The International Conference of Harmonization (ICH) organization (ICH Q3A&ICHQ3B) specified the acceptable concentration limits of various impurities in the pharmaceutical active ingredient (PAI) or in the final dosage forms [2,3]. Determination of the permitted quantity of impurities has also been undertaken by the United States Pharmacopoeia (USP) [4] and the British Pharmacopoeia (BP) [5]. Consequently, both qualitative and quantitative profiling of impurities are getting attention from drug regulatory authorities. The ICH [2] documented that organic impurities are frequently encountered in PAI. Such impurities originate from different sources, namely, unreacted starting or intermediate materials through the synthetic process, presence of by-products, and appearance of degradation products either by degradation of end products or through aging and improper storage of PAI.

Paracetamol (PCA), acetamide, N-(4-hydroxy phenyl) [4] (Table 1), is a potent analgesic and antipyretic drug that is available over-the-counter and could be safely administered to children and elderly patients [6]. Some organic impurities are formed during the synthesis of PCA, including p-amino phenol (PAP) and p-nitro phenol (PNP) (Table 1). Since PCA is synthesized through an acetylation reaction between PAP and acetic anhydride [7], PAP is, thus, considered as a major organic impurity of PCA, where it being the starting material may be found in excess as unreacted form, or it may be present as a degradation product of PCA due to improper storage [7]. PNP may also be present but in a lower extent than PAP [8]. Both USP and BP specify the amount of PAP in PCA pure form to be 0.005% w/w [4,5], while its limit in the final products depends on the type of the dosage form [7]. The significance of PAP quantitation is based on the reported clinical studies of its teratogenic and nephrotoxic effects on humans [9]. On the other hand, PNP is believed to cause methemoglobinemia, a disorder accompanied by lower capability of carrying oxygen to the tissues [10].

Table 1

Chemical structure of the studied compounds

Studied speciesChemical structurepKa
PCA
9.38
PAP
5.48, 10.46
PNP
7.15
PSU
9.52, 13.89
BZH
7.1
BZA
4.2

Pseudoephedrine hydrochloride (PSU) – [(+)-(1s,2s)-2-methyl amino-1-phenyl propan-1-ol]hydrochloride [4] (Table 1) – a stereoisomer of ephedrine and an α adrenergic agonist [11] – is a sympathomimetic amine that is commonly combined with other ingredients for the symptomatic relief of cough and cold [11]. Its uses to control urinary incontinence and for the management of priapism have been documented [11].

Mass production of PSU involves reductive amination of l-phenylacetylcarbinol (l-PAC), and the intermediate product is produced via a biotransformation process using yeast, where benzaldehyde (BZH) acts as a substrate. BZH then condenses with acetaldehyde – which results from decarboxylation of pyruvic acid (a product of glucose glycolysis) by pyruvate decarboxylase, where the product of condensation is proved to be l-PAC [12]. Khan and Daugulis [13] reported benzoic acid (BZA) as a by-product of this synthesis. It is, thus, expected that both BZH and BZA are potential impurities that could be encountered in PSU pharmaceutical formulations.

It is reported that 55–75% of PSU is excreted in urine without any change [11]. Pseudoephedrine elimination half-life is documented to be pH dependent [14]. The presence of BZH or BZA – as impurities in PSU – is expected to modify the pH of the urine, causing a prolongation in the duration of action of PSU. This behavior may in turn intensify the common side effects experienced from sympathomimetic “tachycardia, insomnia, anxiety,” etc.

Simultaneous determination of PCA with both PAP and PNP was performed by applying various separation techniques such as conventional high-performance liquid chromatography (HPLC) [15,16] or by using microemulsion liquid chromatography and micellar electrokinetic capillary chromatography [8]. The assay of PCA with PAP and/or other impurities was carried out using HPLC [7,17,18,19,20], micellar electro kinetic capillary chromatography [21], and thin-layer chromatography densitometry [20,22]. Moreover, some electrochemical methods [23,24,25,26] were also applied to quantify the formerly mentioned analytes.

On the other hand, few reports were about the quantitation of impurities in PSU [27,28,29], where focusing on the determination of PSU itself as an impurity in methamphetamine was prevalent, since PSU is considered as one of the main precursors of methamphetamine synthesis [30]. As a consequence, many countries start to limit the prescription of PSU as an over-the-counter drug, providing a comprehensive measure against methamphetamine trafficking. The proposed method was fully validated, which allows its application for the analysis of different dosage forms containing PCA or PSU. Moreover, a photodegradation study was carried out to prove that the proposed method indicates the stability.

This study depends on using hybrid micelle liquid chromatography (HMLC) instead of applying traditional reversed phase HPLC, as HMLC is superior in many aspects, because it has a unique ability to simultaneously separate the pharmaceuticals carrying various charges and the neutral compounds whose polarities are diverse with distinguished reproducibility and remarkable selectivity, in addition to supporting the universal trend of applying green chemistry in chemical analysis [31]. The HMLC is considered safe for analysts; besides, it is well-known to be ecofriendly. These features arise from the fact that sodium dodecyl sulfate (SDS) is the main component in HMLC, and its safety as a surfactant has been proved [31]. Direct application of SDS to the skin shows negative carcinogenic effects. Besides, it was found to be negative in the bacterial mutation test (Ames test) [32]. Moreover, SDS prevents the evaporation of the small ratios of organic modifiers added to HMLC, which is another advantage to this mobile phase as it reduces the hazards usually encountered in organic–aqueous mobile phases that consume a large amount of organic solvents [31]. Carrying the chemical nature of a fatty alcohol, SDS is liable to be degraded aerobically; consequently, HMLC waste is considered clean. When the analysis does not require a large number of sample injections, the hybrid micelle liquid mobile phase is susceptible to recycling [33]. Owing to the solubilizing power of micelles, the application of HMLC to dosage form extraction and quantification makes it an alternative candidate to the conventional mobile phases [34]. Another advantage which encouraged the authors to utilize HMLC is its compatibility with reversed phase columns and several detection modes [35,36].

In this study, a HMLC method based on UV detection was developed for the simultaneous analysis of either PCA or PSU with their synthetic impurities. The proposed method was validated and applied successfully to assay different pharmaceuticals containing PCA or PSU.

2 Experimental

2.1 Instrumentation

Chromatographic separation was carried out using a Shimadzu SPD-20A apparatus, a product of Kyoto, Japan, provided with a 20 μL loop and a UV/VIS detector. The instrument is supplied with a CTO-20A column oven and a DGU-207 degasser unit. Besides, a pH meter (Jenway, England, UK) was used.

2.2 Materials and reagents

PSU, of purity 99.65%, was provided by Sigma Pharmaceuticals, Cairo, Egypt. PCA, of purity 100.12%, was provided by SEDICO Pharmaceutical Company, Cairo, Egypt. PAP and PNP, having purity percentages of 98% and 99%, respectively, were purchased from Alfa Aesar Fine Chemicals, Fisher Scientific, USA, whereas BZH and BZA were imported from Oxford Lab. Fine Chemical, India.

Methanol and acetonitrile of HPLC grade were obtained from TEDIA Company, Inc., Fairfield, USA. SDS was imported from Sigma Aldrich, USA. Meanwhile, El Nasr Pharmaceutical Chemical Company, Egypt, supplied both O-phosphoric acid and triethylamine (TEA; both with 85% minimum assay).

2.3 Pharmaceutical dosage forms

Cetal® oral drops containing 100 mg of PCA in 1 mL and Cetal® suspension containing 250 mg of micronized PCA in 5 mL were supplied by Egyptian International Pharmaceutical Industries Co., Tenth of Ramadan City, Egypt. Injectamol® solution for IV infusion containing 10 mg PCA/mL was supplied by PHARCO B International for Pharma-Tech Co., Cairo, Egypt. Rhinostop® oral drops containing 25 mg of PSU and 2 mg of carbinoxamine maleate in 1 mL were provided by Medical Union Pharmaceuticals MUP, Egypt. Decongess-L® capsules containing 120 mg of PSU and 5 mg of loratadine were supplied by Pharaonia Pharmaceuticals, Egypt. All pharmaceutics were purchased from local pharmacies in Mansoura, Egypt.

2.4 Chromatographic separation conditions

Both mixtures were separated using a C18 Prontosil Kromaplus column (250 × 4.6 mm; León berg, Germany), which was maintained at 40°C throughout the analysis, applying a flow rate of 1.5 mL/min and adopting UV detection at 240 nm for mixture I (PCA with PAP and PNP) and at 220 nm for mixture II (PSU with BZH and BZA).

For both mixtures, the mobile phase consisted of 0.1 M SDS, acetonitrile, and TEA (90:10:0.3, v/v/v) and adjusted to pH 4 (mixture I) or pH 3.7 (mixture II) using 2 M orthophosphoric acid.

Routine steps aiming to maintain the stability of the chromatographic system were carefully followed, where ultrafiltration of the mobile phase was carried out using Chrom-Tech UK Nylon membrane filters having a pore size of 0.45 µm, followed by sonication for 30 min. After analysis, the system was first washed with deionized double-distilled water for 30 min and then with a mixture of distilled water and methanol in a ratio of 1:1 for another 30 min.

2.5 Calibration curve

All stock solutions were individually prepared as 1.0 mg/mL except for PSU which was prepared as 10.0 mg/mL. Each working standard solution was prepared by serial dilution of its corresponding stock solution in a 10.0 mL volumetric flask using methanol, to cover the linearity ranges of 3.0–100.0, 4.0–200.0, 10.0–400.0, 2.0–100.0, and 3.0–150.0 µg/mL for PCA, PAP, PNP, BZH, and BZA, respectively, and 0.2–3.0 mg/mL for PSU. Each calibration curve was constructed by plotting the final concentration of the analyte – in µg/mL or mg/mL – versus the average response (average peak area obtained by triplicate injection of each concentration). Regression equation for each analyte was deduced from the corresponding calibration curve.

2.6 Analysis of laboratory prepared mixtures

Different volumes of the stock solutions within the linearity range of either PCA with PAP and PNP (mixture I) or PSU with BZH and BZA (mixture II) were transferred to 10.0 mL volumetric flasks and completed to the mark with methanol. The procedures mentioned under “Calibration curve” were then followed to deduce the concentration of each analyte in both mixtures.

2.7 Analysis of different dosage forms

2.7.1 Oral drops and solution for IV infusion

Either 1.0 or 10.0 mL of Cetal® oral drops or Injectamol® solution for IV infusion was transferred to a 100.0 mL volumetric flask and diluted with methanol to the mark. Ten milliliters of Rhinostop® oral drops were transferred to a 25.0 mL volumetric flask and diluted to the volume with methanol. These aliquot volumes were selected to reach the final concentration of the stock solutions of 1.0 mg/mL for PCA and 10.0 mg/mL for PSU.

2.7.2 Capsules

Ten capsules were weighed and evacuated from their content. Capsular content equivalent to 250.0 mg PSU was transferred to a small conical flask and extracted with methanol (2 × 10 mL) with the aid of sonication. The extracts were filtered into a 25.0 mL volumetric flask. Few milliliters of methanol were used to wash the conical flask and complete the volume in the volumetric flask to reach a final stock solution concentration of 10.0 mg/mL.

2.7.3 Suspension

Cetal® suspension was shaken before extraction to avoid the presence of any settled particles, after which 2.0 mL of the suspension was quantitatively transferred to a conical flask, then the extraction steps mentioned for capsules were followed using a 100.0 mL volumetric flask for dilution, so as to prepare a stock solution with the final concentration of 1.0 mg/mL.

The stock solutions of all the extracted dosage forms were subjected to a serial dilution with methanol to prepare different concentrations within the linearity ranges of either PCA or PSU. The concentration of each drug in its pharmaceutical preparation was calculated by referring to its regression equation.

2.8 Photodegradation stability study

Two dosage forms of PCA were selected to carry out this study: Cetal® oral drops and Injectamol® solution for IV infusion (final concentration: 100.0 µg/mL PCA) extracts. Photodegradation procedures were performed with analogy to a previous report [16].

During this study, the methanolic solution of each dosage form was irradiated with a UV lamp (254 nm) for 1 h. The irradiated solutions were assayed using two steps, first immediately after exposure to UV radiation and the second time was 7 days later during this time the solutions were maintained at ambient temperature in the laboratory. In both cases, the solutions were injected in triplicates under the chromatographic conditions described for PCA. Quantitative determination of the analyte was performed by applying the specified regression equation.

  1. Ethical approval: The conducted research is not related to either human or animal use.

3 Results and discussion

Optimization of chromatographic conditions aims to get adequate separation and to quantify the studied drugs together with their impurities. The studied factors for mobile phase optimization include concentration of surfactant, type and ratio of organic modifier, pH of the mobile phase, and the detection wavelength. During optimization of the chromatographic separation conditions for both mixtures, two factors were found to be in common: the column temperature and the flow rate.

To achieve high repeatability, the column thermostat was maintained at 40°C through the analysis, which also assisted in lowering the applied pressure resulting from the organic modifier and the high flow rate [37]. In addition, a flow rate of 1.5 mL/min was found suitable regarding peak shape, so it was utilized during the assay.

Regarding mixture I: PCA with PAP and PNP, it was found that the retention time tr of PCA was not affected by changing the surfactant concentration (from 0.05 to 0.15 M); however, distorted peak shape and poor separation from the solvent front were observed at lower concentrations (0.05–0.075 M), while tr of both PAP and PNP gradually decreases by increasing the SDS molar concentration. The tailing of PAP peak was remarkable when the SDS strength was 0.15 M; therefore, 0.1 M SDS was chosen because it provides reasonable analysis time accompanied by peak symmetry and acceptable baseline separation (Figure 1As–Ds).

The pH of the mobile phase was also studied over the range of 3–6, and it was found that through the entire range, the retention times and peak responses of all three species were slightly affected (Figure 2As–Es), as the studied compounds possess the basic pKa values (Table 1) and are completely ionized through the entire investigated pH range. Better resolution was achieved between the peaks of PCA and PAP at pH value ≥4, however, at pH values ranging from 4.5 to 6, the peaks of all the three analytes were distorted. Based on these findings, this mixture was analyzed at pH 4.

The type and ratio of the organic modifier were also a matter of concern. Both methanol and 1-propanol succeeded in separating PCA from its impurities, but both resulted in distorted PCA peaks and poor baseline separation (Figure 3As and Bs). Acetonitrile, on the other hand, was able to overcome this drawback, providing optimum separation and well-shaped symmetric peaks. The ratio of acetonitrile (7–15%) was also investigated, as expected, by increasing the percentage of acetonitrile, the retention time of both PAP and PNP decreased gradually, while tr of PCA was slightly affected. Although the use of 15% of acetonitrile enhanced the peak response of PAP, it resulted in a forked peak of PCA; thus, 10% acetonitrile was used to maintain the peak symmetry.

To achieve maximum sensitivity, different wavelength settings were tried, ranging from 220 to 270 nm. Despite both 220 and 230 nm resulted in higher sensitivity for both PAP and PNP, they were not used, as they yielded a very pronounced solvent front with poorly separated baseline. On the other hand, higher wavelength values (250–270 nm) enhanced the sensitivity of PCA but depressed that of PAP and PNP. Consequently, 240 nm was chosen to achieve the appropriate sensitivity parameter for the three compounds.

Concerning mixture II: PSU with BZH and BZA, it was found that separation of the three species is pH dependent. When the pH was lower than 3.5, the PSU eluted with the solvent front and poor resolution was obtained between BZH and BZA (Figure 4As). By increasing the pH to values higher than 4 (pH 4.5–5.5), the peaks of BZH and BZA showed poor resolution but the PSU showed acceptable separation from both the analytes (Figure 4Bs). Further elevation in pH (pH ≥ 6) resulted in total overlap of BZH and BZA to appear as a single peak; whereas the PSU elution order was altered, so that it appeared first (Figure 4Cs). Therefore, pH 3.7 was utilized and considered the most suitable for obtaining well-separated peaks. An interpretation of this behavior could be understood by knowing the pKa values of the three compounds (Table 1). The basic pKa values of PSU are 9.52 and 13.89 and its degree of ionization increases by decreasing the pH values. The pH ranges were selected in such a way that the PSU was completely ionized throughout the process. It was observed that at pH values lower than 3.5, PSU was eluted with the mobile phase owing to its increased polarity. Gradual increase in pH leads to depression of PSU ionization, and it was successfully separated under the described chromatographic conditions. On the other hand, the degree of ionization of BZA increases by increasing the pH over its pKa (4.2), and its retention time starts to decrease dramatically to overlap with BZH.

The surfactant concentration was also studied over the range of 0.05–0.18 M. SDS (0.05 M) did not have enough elution strength to separate PSU that overlapped with the solvent front (at pH 3.7; Figure 5As), while higher concentrations succeeded to elute PSU. As a result, 0.1 M SDS was chosen as it achieved well-separated peaks accompanied by a short chromatographic run. An advantage of 0.1 M SDS over 0.075 M SDS was that it also successfully separated the three pharmaceuticals (Figure 5Bs). In spite of the fact that both 0.15 M and 0.18 M SDS succeeded in achieving separation and yielded shorter analysis time, they were not used, as 0.15 M resulted in an overlap of the peaks of BZH and PSU accompanied by distorted peak shapes (Figure 5Cs), while 0.18 M yielded tailed peaks of all three analytes (Figure 5Ds). It is to be noticed that the elution order was modified by using higher concentrations of SDS, i.e., at 0.15 M SDS, PSU eluted after BZH and BZA appeared later. Upon increasing the molar strength to reach 0.18 M, PSU was eluted first, followed by BZH and eventually by BZA.

The type and ratio of the organic modifier were also investigated in this study. The use of methanol did not provide the required separation of the three analytes, where the peaks of BZH and BZA were distorted and PSU had a long retention time (25 min), in addition to the poor baseline separation (Figure 6As). On the other hand, upon using 1-propanol, it was not possible to separate BZH from BZA as they appeared as a single peak; furthermore, the elution order was modified, where PSU appeared first followed by an overlapped peak of the two impurities (Figure 6Bs). Acetonitrile was the solvent of choice, as it could overcome the drawbacks of the two previous organic modifiers. Its ratio (7–15%) was also investigated to yield optimum separation parameters. It was found that tr of the three compounds decreased upon increasing the ratio of acetonitrile through this range, so 10% was chosen to yield a shorter chromatographic run and well-shaped separated peaks. To achieve the best sensitivity measures, 220 nm was adopted as a detection wavelength.

TEA is added to HMLC for two reasons, first to adjust the pH and second to increase the separation efficiency [31] through binding to the silanol groups of the stationary phase, causing a synergistic effect with the organic modifier in enhancing the efficiency. The effect of TEA percentage on separation efficiency of the proposed method was studied, and 0.3% was found to be the optimum ratio, as higher percentages (0.4–1%) cause elution of PCA with solvent front (mixture I) and poor resolution between PSU and its impurities (mixture II). Meanwhile, lower ratios of TEA resulted in asymmetric peaks for all the chemical compounds in both mixtures.

A representative chromatogram of PCA with its two impurities, PAP and PNP, is illustrated in Figure 1A, where separation was conducted using 0.1 M SDS, acetonitrile, and TEA (90:10:0.3, v/v/v) at pH 4 by adopting UV detection at 240 nm, using a flow rate of 1.5 mL/min, and maintaining the column at 40°C.

Figure 1 (A) A chromatogram representing PCA with its impurities PAP and PNP under the described chromatographic conditions, where (a) 25.0 µg/mL PCA, (b) 10.0 µg/mL PAP, and (c) 20.0 µg/mL PNP. (B) A chromatogram representing PSU with its impurities BZH and BZA under the described chromatographic conditions, where (a) 10.0 µg/mL BZH, (b) 10.0 µg/mL BZA, and (c) 1.0 mg/mL PSU.
Figure 1

(A) A chromatogram representing PCA with its impurities PAP and PNP under the described chromatographic conditions, where (a) 25.0 µg/mL PCA, (b) 10.0 µg/mL PAP, and (c) 20.0 µg/mL PNP. (B) A chromatogram representing PSU with its impurities BZH and BZA under the described chromatographic conditions, where (a) 10.0 µg/mL BZH, (b) 10.0 µg/mL BZA, and (c) 1.0 mg/mL PSU.

Figure 1B represents a chromatogram of PSU with its two impurities, BZH and BZA, where separation was carried out using a mobile phase composed of 0.1 M SDS, acetonitrile, and TEA (90:10:0.3, v/v/v) at pH 3.7, adopting 220 nm as a detection wavelength, and using a flow rate of 1.5 mL/min, where the column temperature was maintained at 40°C.

3.1 Method validation

According to the USP [4], validation is the establishment of any analytical method through laboratory studies to ensure that the performance of the suggested method is in accordance with the preconceived application. The typical characteristics in method validation include linearity and range, limit of detection (LOD), limit of quantitation (LOQ), accuracy, precision, specificity, and robustness.

For mixture I, linearity was experienced over the range of 3.0–100.0, 4.0–200.0, and 10.0–400.0 µg/mL, for PCA, PAP, and PNP, respectively, with their corresponding LOD values of 1.5, 2.0, and 5.0 µg/mL and LOQ values of 2.5, 3.0, and 9.0 µg/mL. Regarding mixture II, the obtained linearity ranges were 2.0–100.0, 3.0–150.0 µg/mL, and 0.2–3.0 mg/mL for BZH, BZA, and PSU, respectively, with their corresponding LOD values of 1.0, 1.5, and 100.0 µg/mL and LOQ values of 1.5, 2.5, and 150.0 µg/mL. Both LOD and LOQ were experimentally determined through evaluating the concentrations which yield a signal–noise ratio of 3:1 and 10:1, respectively [4]. The low values obtained demonstrate the sensitivity of the proposed method.

Evaluation of the accuracy is performed through comparison of the concentrations of the studied compounds in both mixtures – whether alone or in laboratory prepared mixtures – applying both the proposed and the reference methods [15,27]. The high accuracy of the proposed method is demonstrated from the small values of t test and variance ratio F test [38]. Tables 2 and 3 list the obtained data where the concentrations were calculated from the regression equation of each drug.

Table 2

Determination of the studied compounds in their pure form by applying the proposed method

ParameterConcentration taken (µg/mL)Concentration found (µg/mL)% foundReference methods [15,27], % found
Mixture I
PCA3.02.9498.1599.47
10.09.8698.5599.22
30.029.8499.46101.57
50.049.9999.97
70.070.31100.44
100.0100.13100.13
Average ± SD99.45 ± 0.92100.09 ± 1.29
t test0.88*
F test1.97*
PAP4.04.01100.2599.64
20.020.37101.84100.84
70.071.15101.64101.28
120.0118.9899.15
150.0149.5199.67
200.0199.7899.89
Average ± SD100.41 ± 1.09100.59 ± 0.85
t test0.92*
F test1.64*
PNP10.09.8598.4798.35
100.098.0598.0599.48
150.0149.5199.67101.47
200.0198.2299.11
300.0302.76100.92
400.0402.96100.74
Average ± SD99.49 ± 1.1799.77 ± 1.58
t test0.83*
F test1.82*
Mixture II
PSU200.0196.5298.2598.16
500.0493.8598.7799.73
1000.0993.4199.3499.33
1500.01485.9299.06
2000.01963.2298.16
3000.03013.51100.45
Average ± SD99.01 ± 0.8499.07 ± 0.82
t test0.24*
F test1.05*
BZH2.01.9999.3399.34
20.019.7498.7299.87
30.029.4298.06101.28
50.049.0698.11
70.071.15101.64
100.0101.28101.28
Average ± SD99.52 ± 1.57100.16 ± 1.01
t test0.79*
F test2.42*
BZA3.03.05101.75100.48
20.020.27101.35101.84
50.050.04100.0899.58
70.069.7799.67
100.099.1599.15
150.0148.9899.32
Average ± SD100.22 ± 1.09100.63 ± 1.14
t test0.24*
F test1.09*

*The tabulated t and F values are 2.571 and 19.30, respectively, at p = 0.05 [38].

Table 3

Determination of the studied drugs in laboratory prepared mixtures using the proposed method

Mixture I
ParameterTaken (µg/mL)% foundReference method [15], % found
PCAPAPPNPPCAPAPPNPPCAPAPPNP
100.010.020.099.5299.78100.77100.85101.78100.33
90.09.018.098.6498.6498.6899.4599.65101.25
80.08.015.0100.6798.2598.7399.35100.1799.25
70.07.015.0101.0899.6799.03
60.06.010.0100.76100.1499.45
Average100.1399.2999.3399.88100.53100.28
SD1.020.810.860.841.11.01
t test*0.640.570.84
F test*1.471.641.45
F test3.743.181.68
Mixture II
ParameterTaken (µg/mL)% foundReference method [27], % found
PSUBZHBZAPSUBZHBZAPSUBZHBZA
3000.030.030.0101.25100.95100.7899.45101.54100.64
2000.020.020.0101.88101.7599.62100.05100.7299.58
1000.010.010.0100.7599.4599.55100.3699.7899.07
800.08.08.0100.0698.4598.25
500.05.05.099.6898.1198.32
Average100.7299.7499.3199.95100.6899.76
SD0.891.571.050.460.880.81
t test0.780.680.72
F test3.743.181.68

*The tabulated t and F values are 2.776 and 19.25, respectively, at p = 0.05 [38].

According to USP [4], precision is the agreement among the obtained results when the analytical procedure is repeatedly applied on multiple homogenous samples. Assessment of precision was carried out by applying the proposed method on three different concentrations of each drug in both mixtures on the same day or on three different days. The data abridged in Table 4 illustrate acceptable precision as revealed from the small values of standard deviation.

Table 4

Precision data of the studied drugs using the proposed method

ParameterIntraday precision
Mixture IMixture II
Taken (µg/mL)% foundTaken (µg/mL)% found
PCAPAPPNPPCAPAPPNPPSUBZHBZAPSUBZHBZA
3.04.010.099.8599.45100.48200.02.03.098.78101.5899.78
50.0100.0200.098.7898.77101.061500.050.075.098.36101.4498.91
100.0200.0400.099.36100.0699.323000.0100.0150.099.7899.67101.58
Mean*99.3399.43100.2998.97100.89100.09
SD0.540.650.890.731.061.36
ParameterInterday precision
Mixture IMixture II
Taken (µg/mL)% foundTaken (µg/mL)% found
PCAPAPPNPPCAPAPPNPPSUBZHBZAPSUBZHBZA
3.04.010.099.65100.0898.78200.02.03.0101.7599.75100.46
50.0100.0200.098.77101.5899.631500.050.075.0100.3598.67101.35
100.0200.0400.0101.4899.4699.453000.0100.0150.099.65101.2599.13
Mean99.97100.3799.29100.5899.89100.31
SD1.381.090.451.071.291.12

  1. *Each value represents the average of three determinations.

Specificity is the ability to assay the analytes in the presence of expected components such as impurities, degradation products, and matrix components [4], and it was clearly manifested in this study.

The specificity of the proposed method could be demonstrated from the adequate separation of PCA and PSU from their impurities (Figure 1A and B). Moreover, the three selected chromatograms from the studied dosage forms (Figure 2A–C) illustrate the satisfactory separation of both drugs from inactive ingredients and separation of PSU from its coformulated pharmaceuticals. Furthermore, acceptable separation of PCA from its photolytic degradation product obtained after UV decomposition of pharmaceutical dosage forms containing PCA (Figure 3A–D) proves the specificity of the proposed method.

Figure 2 (A) A chromatogram representing Cetal® oral drop extracts, where (a) 50.0 µg/mL PCA and (b) minor impurity. (B) A chromatogram representing Rhinostop® oral drop extracts, where (a) 80.0 µg/mL carbinoxamine maleate and (b) 1.0 mg/mL PSU. (C) A chromatogram representing Decongess-L® capsule extracts, where (a) 41.67 µg/mL loratadine and (b) 1.0 mg/mL PSU.
Figure 2

(A) A chromatogram representing Cetal® oral drop extracts, where (a) 50.0 µg/mL PCA and (b) minor impurity. (B) A chromatogram representing Rhinostop® oral drop extracts, where (a) 80.0 µg/mL carbinoxamine maleate and (b) 1.0 mg/mL PSU. (C) A chromatogram representing Decongess-L® capsule extracts, where (a) 41.67 µg/mL loratadine and (b) 1.0 mg/mL PSU.

Figure 3 (A) A chromatogram representing PCA (100.0 µg/mL) in Cetal® oral drop extracts after exposure to UV light for 1 h, where (a) PCA and (b) photolytic degradation product. (B) A chromatogram representing PCA (100.0 µg/mL) in the extract of Injectamol® solution for IV infusion after exposure to UV light for 1 h, where (a) PCA and (b) photolytic degradation product. (C) A chromatogram representing PCA (100.0 µg/mL) in Cetal® oral drop extracts after exposure to UV light for 1 h and leaving the solution for 7 days in the laboratory, where (a) PCA and (b) photolytic degradation product. (D) A chromatogram representing PCA (100.0 µg/mL) in the extract of Injectamol® solution for IV infusion after exposure to UV light for 1 h and leaving the solution for 7 days in the laboratory, where (a) PCA and (b) photolytic degradation product.
Figure 3

(A) A chromatogram representing PCA (100.0 µg/mL) in Cetal® oral drop extracts after exposure to UV light for 1 h, where (a) PCA and (b) photolytic degradation product. (B) A chromatogram representing PCA (100.0 µg/mL) in the extract of Injectamol® solution for IV infusion after exposure to UV light for 1 h, where (a) PCA and (b) photolytic degradation product. (C) A chromatogram representing PCA (100.0 µg/mL) in Cetal® oral drop extracts after exposure to UV light for 1 h and leaving the solution for 7 days in the laboratory, where (a) PCA and (b) photolytic degradation product. (D) A chromatogram representing PCA (100.0 µg/mL) in the extract of Injectamol® solution for IV infusion after exposure to UV light for 1 h and leaving the solution for 7 days in the laboratory, where (a) PCA and (b) photolytic degradation product.

The robustness, which measures the capacity of the analytical method to be unaffected by the minor changes in the experimental conditions indicating its suitability through normal analysis conditions [4], could be illustrated in this study. This could be exemplified by referring to the optimization of mixture I, where the pH did not affect the retention times or the sensitivity of the three compounds, and the ability to use a variety of organic modifiers to separate them efficiently in spite of selecting acetonitrile; while in the case of mixture II, wide concentration range of SDS could be applied (0.1–0.18 M) to separate PSU from its impurities.

3.2 Applications

3.2.1 Analysis of PCA and PSU in their dosage forms

The proposed method succeeded to quantitate PCA and PSU in their different pharmaceutical dosage forms (Figure 2A–C and Table 5). As the presented chromatograms demonstrated, the coformulated pharmaceuticals with PSU, carbinoxamine maleate and loratadine (Figure 2B and C), did not interfere with the separation or quantification of PSU as revealed from their retention times (8.2 and 4.6 min, respectively). On other hand, the sample matrix was not an obstacle in PCA assay (Figure 2A). These facts emphasize on the specificity of the proposed method; moreover, the high recovery percentages and the low values of t and F tests confirm the accuracy of the method.

Table 5

Application of the proposed method to the analysis of the studied drugs in their pharmaceuticals

ParameterTaken (µg/mL)Found (µg/mL)% foundReference methods [15,27], % found
Cetal® oral drops10.09.8598.5498.77
30.029.4598.1699.58
50.049.9299.8499.36
70.069.5299.32
100.0100.48100.48
Mean ± SD99.27 ± 0.9499.24 ± 0.42
t*0.44
F*5.01
Cetal® suspension10.09.9799.66101.44
30.029.7499.13100.85
50.050.87101.74100.32
70.071.27101.81
100.0100.29100.29
Mean ± SD100.53 ± 1.21100.87 ± 0.56
T0.21
F4.7
Injectamol® solution for IV infusion10.09.8898.77100.78
30.029.6998.9899.37
50.050.74101.4799.81
70.070.08100.11
100.0100.37100.37
Mean ± SD99.94 ± 1.199.99 ± 0.72
T0.46
F2.33
Rhinostop® oral drops1000.099999.85100.97
1500.01,522101.47101.48
2000.02,027101.3599.61
2500.02,512100.46
3000.02,99399.78
Mean ± SD100.58 ± 0.81100.69 ± 0.97
T0.18
F1.43
Decongess-L® capsules1000.099699.6199.75
1500.01,48699.0599.61
2000.02,009100.47100.47
2500.02,534101.37
3000.03,032101.05
Mean ± SD100.31 ± 0.9799.94 ± 0.46
T0.29
F4.45

*The tabulated t and F values are 2.776 and 19.25, respectively, at p = 0.05 [38].

No impurities were detected in any of the tested pharmaceutical formulations of PSU (Figure 2B and C), while a minor impurity was observed at 2.7 min in PCA pharmaceuticals (Figure 2A).

3.2.2 Stability-indicating property of the proposed method

By analogy to a previous report [16], a forced degradation study was performed to assess the stability-indicating nature of the proposed method. Upon exposing methanolic solutions of Cetal® oral drops or Injectamol® solution for IV infusion (final concentration: 100.0 µg/mL PCA) to a UV lamp at 254 nm for 1 h (Figure 3A and B), the degradation product which appeared in PCA dosage forms at 2.7 min was still persistent. When the same irradiated solutions were tested later after keeping them at controlled temperature in the laboratory for a period of 7 days, a remarkable increase in the concentration of the produced degradation product was detected as revealed from the enhancement in its peak area (Figure 3C and D). According to Martignac et al. [39], photolysis of PCA in the presence of oxygen suggests the formation of 4-aminophenol, which undergoes further oxidation to p-benzoquinone (Figure 4).

Figure 4 Proposed pathway of the photolytic degradation of PCA.
Figure 4

Proposed pathway of the photolytic degradation of PCA.

The significance of carrying out this stability study arises from the fact of the ecotoxicity of the photodegradation product of PCA, which has been studied by Sugihara [40] via the luminescent bacteria test after exposing PCA to UV light. Hence, the proposed method serves as both a qualitative and a quantitative tool of this toxic product, aiming to protect the ecosystem and improve public health.

Selection of UVC radiation (254 nm) for photolysis of PCA was made in accordance with a previous report which proved inefficient photodegradation of PCA by UVA (315–400 nm) or by UVB (280–315 nm) [41], as UVC has a high potential energy and consequently shows more photolysis efficiency.

On the other hand, PSU was not a subject of concern in this stability study, owing to its high stability and resistance to photolytic degradation as reported in its monograph on analytical profile for drug substances [42].

4 Conclusion

A HMLC method was developed for the simultaneous determination of PCA and PSU with some of their synthetic impurities. The method was subjected to full validation, which enables its application to analysis of the concerned drugs in their pharmaceuticals; moreover, photodegradation of PCA was carried out to prove the stability-indicating property of the proposed method. The proposed method carries many advantages over the reported articles, as for example the short chromatographic run especially for mixture I, where the separation of the three studied drugs was accomplished in 9 min. This is superior to other reports using conventional aqueous–organic HPLC techniques where PNP causes a delay in the chromatographic run time, 33.37 min [15] and 12 min [16]. Besides, better resolution was achieved between PCA and PAP in the proposed method unlike other research from the literature [18]. These facts illustrate the contribution of this work to the field of drug analysis and emphasize on its significance.

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  1. Conflict of interest: The authors declare no conflict of interest.

References

[1] Nageswara Rao R, Nagaraju V. An overview of the recent trends in development of HPLC methods for determination of impurities in drugs. J Pharm Biomed Anal. 2003;33:335–77.10.1016/S0731-7085(03)00293-0Suche in Google Scholar

[2] International Conferences on Harmonization, Revised Guidance on Impurities in New Drug Substances. Q3A(R). Federal Register; 2000. vol. 65. p. 45085–90.Suche in Google Scholar

[3] International Conferences on Harmonization, Revised guidance on impurities in new drug products. Q3B(R). Federal Register; 2000. vol. 65. p. 44791–7.Suche in Google Scholar

[4] United States Pharmacopeial Convention: United States Pharmacopoeia 30; National Formulary 25. US Pharmacopoeia Convention.Suche in Google Scholar

[5] “The British Pharmacopoeia” The Stationary Office: London, (2009), Electronic version.Suche in Google Scholar

[6] Brunton LL. Goodman and Gilman’s: the pharmacological basis of therapeutics, 12th edn. California, United States: Mc-Graw Hill; 2011.Suche in Google Scholar

[7] Sornchaithawatwong C, Vorrarat S, Nunthanavanit P. Simultaneous determination of paracetamol and its main degradation product in generic paracetamol tablets using reverse phase HPLC. J Health Res. 2010;24:103–6.Suche in Google Scholar

[8] McEvoy E, Donegan S, Power J, Altria K. Application of MELC and MEEKC for the analysis of paracetamol and related impurities in suppositories. Chromatographia. 2008;68:49–56.10.1365/s10337-008-0642-2Suche in Google Scholar

[9] Song H, Chen TS. P-Aminophenol-induced liver toxicity: tentative evidence of a role for acetaminophen. J Biochem Mol Toxicol. 2001;15:34–40.10.1002/1099-0461(2001)15:1<34::AID-JBT4>3.0.CO;2-USuche in Google Scholar

[10] ATSDR-agency for toxic substances and disease registry. Toxocological profile for nitrophenol. U.S. public health service in collaboration with U.S. environmental protection agency EPA; 1992. https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=880&tid=172Suche in Google Scholar

[11] Sweetman SC. Martindale: the complete drug reference, 36th edn. London, UK: Pharmaceutical Press; 2009.Suche in Google Scholar

[12] Miguez M, Nunes P, Azeredo N, Pedraza SF, Vasconcelos M, Viana O, et al. Selection of yeasts for the production of l-phenyl-acetilcarbinol by biotransformation in shake flasks. Chem Engin Trans. 2012;27:163–8.Suche in Google Scholar

[13] Khan TR, Daugulis AJ. The effects of polymer phase ratio and feeding strategy on solid-liquid TPPBs for the production of l-phenylacetylcarbinol from benzaldehyde using Candida utilis. Biotechnol Lett. 2011;33:63–70.10.1007/s10529-010-0408-4Suche in Google Scholar

[14] Brater DC, Kaojarern S, Benet LZ, Lin ET, Lockwood T, Morris RC, et al. Renal excretion of pseudoephedrine. Clin Pharmacol Ther. 1980;28:690–4.10.1038/clpt.1980.222Suche in Google Scholar

[15] Nagewara Rao R, Narasaraju A. Rapid separation and determination of process-related substances of paracetamol using reversed phase HPLC with photo diode array as a detector. Anal Sci. 2006;22:287–92.10.2116/analsci.22.287Suche in Google Scholar

[16] Calinescu O, Badea IA, Vladescu L, Meltzer V, Pincu E. HPLC separation of acetaminophen and its impurities using a mixed-mode reversed-phase/cation exchange stationary phase. J Chromatog Sci. 2012;50:335–42.10.1093/chromsci/bmr043Suche in Google Scholar

[17] AkAay C, Degim IT, Sayal A, Aydin A, Ozkan Y. GUL HRapid and simultaneous determination of acetylsalicylic acid, paracetamol, and their degradation and toxic impurity products by HPLC in pharmaceutical dosage forms. Turk J Med Sci. 2008;38:167–73.Suche in Google Scholar

[18] Monser L, Darghouth F. Simultaneous LC determination of paracetamol and related compounds in pharmaceutical formulations using a carbon-based column. J Pharm Biomed Anal. 2002;27:851–60.10.1016/S0731-7085(01)00515-5Suche in Google Scholar

[19] Kamberi M, Riley CM, Ma X, Huang C-WC. A validated, sensitive HPLC method for the determination of trace impurities in acetaminophen drug substance. J Pharm Biomed Anal. 2004;34:123–8.10.1016/j.japna.2003.08.015Suche in Google Scholar

[20] Abdelaleem EA, Naguib IA, Hassan ES, Ali NW. HPTLC and RP-HPLC methods for simultaneous determination of paracetamol and pamabrom in presence of their potential impurities. J Pharm Biomed Anal. 2015;114:22–7.10.1016/j.jpba.2015.04.043Suche in Google Scholar

[21] Nemeth T, Jankovics P, Nemeth-Palotas J, Koszegi-Szalai H. Determination of paracetamol and its main impurity 4-aminophenol in analgesic preparations by micellar electrokinetic chromatography. J Pharm Biomed Anal. 2008;47:746–9.10.1016/j.jpba.2008.03.003Suche in Google Scholar PubMed

[22] Abdelaleem EA, Abdelwahab NS. Stability-indicating TLC–densitometric method for simultaneous determination of paracetamol and chlorzoxazone and their toxic impurities. J Chromatog Sci. 2013;51:187–91.10.1093/chromsci/bms125Suche in Google Scholar PubMed

[23] Shiroma LY, Santhiago M, Gobbi AL, Kubota LT. Separation and electrochemical detection of paracetamol and 4-aminophenol in a paper-based microfluidic device. Anal Chim Acta. 2012;725:44–50.10.1016/j.aca.2012.03.011Suche in Google Scholar PubMed

[24] Yin H, Shang K, Meng X, Ai S. Voltammetric sensing of paracetamol, dopamine and 4-aminophenol at a glassy carbon electrode coated with gold nanoparticles and an organophilic layered double hydroxide. Microchim Acta. 2011;175:39–46.10.1007/s00604-011-0652-xSuche in Google Scholar

[25] Safavi A, Maleki N, Moradlou O. A selective and sensitive method for simultaneous determination of traces of paracetamol and p-aminophenol in pharmaceuticals using carbon ionic liquid electrode. Electroanalysis. 2008;20:2158–162.10.1002/elan.200804292Suche in Google Scholar

[26] Kong F-Y, Gu S-X, Wang J-Y, Fang H-L, Wang W. Facile green synthesis of graphene–titanium nitride hybrid nanostructure for the simultaneous determination of acetaminophen and 4-aminophenol. Sens Actuators B Chem. 2015;213:397–403.10.1016/j.snb.2015.02.120Suche in Google Scholar

[27] Ekpe A, Tong JH, Rodriguez L. High-performance liquid chromatographic method development and validation for the simultaneous quantitation of naproxen sodium and pseudoephedrine hydrochloride impurities. J Chromatog Sci. 2001;39:81–6.10.1093/chromsci/39.3.81Suche in Google Scholar PubMed

[28] Duddu SP, Mehvar R, Grant DJW. Liquid chromatographic analysis of the enantiomeric impurities in various pseudoephedrine samples. Pharm Res. 1991;8:1430–3.10.1023/A:1015813509816Suche in Google Scholar

[29] Abdelwahab NS, Abdelaleem EA. Stability indicating RP-HPLC method for simultaneous determination of guaifenesin and pseudoephedrine hydrochloride in the presence of syrup excipients. Arab J Chem. 2017;10:S2896–901.10.1016/j.arabjc.2013.11.019Suche in Google Scholar

[30] Armellin S, Brenna E, Frigoli S, Fronza G, Fuganti C, Mussida D. Determination of the synthetic origin of methamphetamine samples by 2H NMR spectroscopy. Anal Chem. 2006;78:3113–7.10.1021/ac052105wSuche in Google Scholar PubMed

[31] El-Shaheny RN, El-Maghrabey MH, Belal FF. Micellar liquid chromatography from green analysis perspective. Open Chem. 2015;13:877–92.10.1515/chem-2015-0101Suche in Google Scholar

[32] CIR Publication. Final report on the safety assessment of sodium lauryl sulfate and ammonium lauryl sulfate. Int J Toxicol. 1983;2:127–81.Suche in Google Scholar

[33] Thomas ORT, White GF. Metabolic pathway for the biodegradation of sodium dodecyl sulphate by Pseudomonas sp-c12b. Biotechnol Appl Biochem. 1989;11:318–27.Suche in Google Scholar

[34] Esteve-Romero J, Carda-Broch S, Gil-Agustí M, Capella-Peiró ME, Bose D. Micellar liquid chromatography for the determination of drug materials in pharmaceutical preparations and biological samples. Trends Anal Chem. 2005;24:75–91.10.1016/j.trac.2004.11.003Suche in Google Scholar

[35] Madamba-Tan LS, Strasters JK, Khaledi MG. Gradient elution in micellar liquid chromatography. I. Micelle concentration gradient. J Chromatogr A. 1994;683:321–34.10.1016/0021-9673(94)00450-1Suche in Google Scholar

[36] Madamba-Tan LS, Strasters JK, Khaledi MG. Gradient elution in micellar liquid chromatography. II. Organic modifier gradients. J Chromatogr A. 1994;683:335–45.10.1016/0021-9673(94)00451-XSuche in Google Scholar

[37] Katz E, Ogan K, Scot RPW. Effect of pressure on solute diffusivity, solvent viscosity and column temperature in liquid chromatography. J Chromatogr A. 1983;260:277–95.10.1016/0021-9673(83)80037-5Suche in Google Scholar

[38] Miller JN, Miller JC. Statistics and chemometrics for analytical chemistry. Harlow, England: Prentice Hall, Pearson; 2010.Suche in Google Scholar

[39] Martignac M, Oliveros E, Maurette M-T, Claparols C, Benoit-Marquié F. Mechanistic pathways of the photolysis of paracetamol in aqueous solution: an example of photo-Fries rearrangement. Photochem Photobiol Sci. 2013;12:527–35.10.1039/C2PP25341KSuche in Google Scholar

[40] Sugihara K. Effect of environmental factors on the ecotoxicity of pharmaceuticals and personal care products. Yakugaku Zasshi. 2018;138:277–80.10.1248/yakushi.17-00177-2Suche in Google Scholar

[41] Xu B, Zhan G, Xu B, Du H, Luo H, Wang T, et al. Degradation of acetaminophen in aqueous solution by UV and UV-activated sludge processes. Water Sci Technol. 2018;78:2088–95.10.2166/wst.2018.483Suche in Google Scholar

[42] Benezra SA, McRae JW. Pseudoephedrine hydrochloride. Anal Profiles Drug Substances. 1979;8:489–507.10.1016/S0099-5428(08)60126-4Suche in Google Scholar

Received: 2019-12-21
Revised: 2020-02-14
Accepted: 2020-02-17
Published Online: 2020-05-23

© 2020 Dina El Sherbiny and Mary E. K. Wahba, published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  88. Effect of isovalent substitution on the crystal structure and properties of two-slab indates BaLa2−xSmxIn2O7
  89. Synthesis, spectral and thermo-kinetics explorations of Schiff-base derived metal complexes
  90. An improved reduction method for phase stability testing in the single-phase region
  91. Comparative analysis of chemical composition of some commercially important fishes with an emphasis on various Malaysian diets
  92. Development of a solventless stir bar sorptive extraction/thermal desorption large volume injection capillary gas chromatographic-mass spectrometric method for ultra-trace determination of pyrethroids pesticides in river and tap water samples
  93. A turbidity sensor development based on NL-PI observers: Experimental application to the control of a Sinaloa’s River Spirulina maxima cultivation
  94. Deep desulfurization of sintering flue gas in iron and steel works based on low-temperature oxidation
  95. Investigations of metallic elements and phenolics in Chinese medicinal plants
  96. Influence of site-classification approach on geochemical background values
  97. Effects of ageing on the surface characteristics and Cu(ii) adsorption behaviour of rice husk biochar in soil
  98. Adsorption and sugarcane-bagasse-derived activated carbon-based mitigation of 1-[2-(2-chloroethoxy)phenyl]sulfonyl-3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl) urea-contaminated soils
  99. Antimicrobial and antifungal activities of bifunctional cooper(ii) complexes with non-steroidal anti-inflammatory drugs, flufenamic, mefenamic and tolfenamic acids and 1,10-phenanthroline
  100. Application of selenium and silicon to alleviate short-term drought stress in French marigold (Tagetes patula L.) as a model plant species
  101. Screening and analysis of xanthine oxidase inhibitors in jute leaves and their protective effects against hydrogen peroxide-induced oxidative stress in cells
  102. Synthesis and physicochemical studies of a series of mixed-ligand transition metal complexes and their molecular docking investigations against Coronavirus main protease
  103. A study of in vitro metabolism and cytotoxicity of mephedrone and methoxetamine in human and pig liver models using GC/MS and LC/MS analyses
  104. A new phenyl alkyl ester and a new combretin triterpene derivative from Combretum fragrans F. Hoffm (Combretaceae) and antiproliferative activity
  105. Erratum
  106. Erratum to: A one-step incubation ELISA kit for rapid determination of dibutyl phthalate in water, beverage and liquor
  107. Review Articles
  108. Sinoporphyrin sodium, a novel sensitizer for photodynamic and sonodynamic therapy
  109. Natural products isolated from Casimiroa
  110. Plant description, phytochemical constituents and bioactivities of Syzygium genus: A review
  111. Evaluation of elastomeric heat shielding materials as insulators for solid propellant rocket motors: A short review
  112. Special Issue on Applied Biochemistry and Biotechnology 2019
  113. An overview of Monascus fermentation processes for monacolin K production
  114. Study on online soft sensor method of total sugar content in chlorotetracycline fermentation tank
  115. Studies on the Anti-Gouty Arthritis and Anti-hyperuricemia Properties of Astilbin in Animal Models
  116. Effects of organic fertilizer on water use, photosynthetic characteristics, and fruit quality of pear jujube in northern Shaanxi
  117. Characteristics of the root exudate release system of typical plants in plateau lakeside wetland under phosphorus stress conditions
  118. Characterization of soil water by the means of hydrogen and oxygen isotope ratio at dry-wet season under different soil layers in the dry-hot valley of Jinsha River
  119. Composition and diurnal variation of floral scent emission in Rosa rugosa Thunb. and Tulipa gesneriana L.
  120. Preparation of a novel ginkgolide B niosomal composite drug
  121. The degradation, biodegradability and toxicity evaluation of sulfamethazine antibiotics by gamma radiation
  122. Special issue on Monitoring, Risk Assessment and Sustainable Management for the Exposure to Environmental Toxins
  123. Insight into the cadmium and zinc binding potential of humic acids derived from composts by EEM spectra combined with PARAFAC analysis
  124. Source apportionment of soil contamination based on multivariate receptor and robust geostatistics in a typical rural–urban area, Wuhan city, middle China
  125. Special Issue on 13th JCC 2018
  126. The Role of H2C2O4 and Na2CO3 as Precipitating Agents on The Physichochemical Properties and Photocatalytic Activity of Bismuth Oxide
  127. Preparation of magnetite-silica–cetyltrimethylammonium for phenol removal based on adsolubilization
  128. Topical Issue on Agriculture
  129. Size-dependent growth kinetics of struvite crystals in wastewater with calcium ions
  130. The effect of silica-calcite sedimentary rock contained in the chicken broiler diet on the overall quality of chicken muscles
  131. Physicochemical properties of selected herbicidal products containing nicosulfuron as an active ingredient
  132. Lycopene in tomatoes and tomato products
  133. Fluorescence in the assessment of the share of a key component in the mixing of feed
  134. Sulfur application alleviates chromium stress in maize and wheat
  135. Effectiveness of removal of sulphur compounds from the air after 3 years of biofiltration with a mixture of compost soil, peat, coconut fibre and oak bark
  136. Special Issue on the 4th Green Chemistry 2018
  137. Study and fire test of banana fibre reinforced composites with flame retardance properties
  138. Special Issue on the International conference CosCI 2018
  139. Disintegration, In vitro Dissolution, and Drug Release Kinetics Profiles of k-Carrageenan-based Nutraceutical Hard-shell Capsules Containing Salicylamide
  140. Synthesis of amorphous aluminosilicate from impure Indonesian kaolin
  141. Special Issue on the International Conf on Science, Applied Science, Teaching and Education 2019
  142. Functionalization of Congo red dye as a light harvester on solar cell
  143. The effect of nitrite food preservatives added to se’i meat on the expression of wild-type p53 protein
  144. Biocompatibility and osteoconductivity of scaffold porous composite collagen–hydroxyapatite based coral for bone regeneration
  145. Special Issue on the Joint Science Congress of Materials and Polymers (ISCMP 2019)
  146. Effect of natural boron mineral use on the essential oil ratio and components of Musk Sage (Salvia sclarea L.)
  147. A theoretical and experimental study of the adsorptive removal of hexavalent chromium ions using graphene oxide as an adsorbent
  148. A study on the bacterial adhesion of Streptococcus mutans in various dental ceramics: In vitro study
  149. Corrosion study of copper in aqueous sulfuric acid solution in the presence of (2E,5E)-2,5-dibenzylidenecyclopentanone and (2E,5E)-bis[(4-dimethylamino)benzylidene]cyclopentanone: Experimental and theoretical study
  150. Special Issue on Chemistry Today for Tomorrow 2019
  151. Diabetes mellitus type 2: Exploratory data analysis based on clinical reading
  152. Multivariate analysis for the classification of copper–lead and copper–zinc glasses
  153. Special Issue on Advances in Chemistry and Polymers
  154. The spatial and temporal distribution of cationic and anionic radicals in early embryo implantation
  155. Special Issue on 3rd IC3PE 2020
  156. Magnetic iron oxide/clay nanocomposites for adsorption and catalytic oxidation in water treatment applications
  157. Special Issue on IC3PE 2018/2019 Conference
  158. Exergy analysis of conventional and hydrothermal liquefaction–esterification processes of microalgae for biodiesel production
  159. Advancing biodiesel production from microalgae Spirulina sp. by a simultaneous extraction–transesterification process using palm oil as a co-solvent of methanol
  160. Topical Issue on Applications of Mathematics in Chemistry
  161. Omega and the related counting polynomials of some chemical structures
  162. M-polynomial and topological indices of zigzag edge coronoid fused by starphene
https://doi.org/10.1515/chem-2020-0041
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paracetamol; pseudoephedrine; impurities; degradation; micellar
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Artikel in diesem Heft

  1. Regular Articles
  2. Electrochemical antioxidant screening and evaluation based on guanine and chitosan immobilized MoS2 nanosheet modified glassy carbon electrode (guanine/CS/MoS2/GCE)
  3. Kinetic models of the extraction of vanillic acid from pumpkin seeds
  4. On the maximum ABC index of bipartite graphs without pendent vertices
  5. Estimation of the total antioxidant potential in the meat samples using thin-layer chromatography
  6. Molecular dynamics simulation of sI methane hydrate under compression and tension
  7. Spatial distribution and potential ecological risk assessment of some trace elements in sediments and grey mangrove (Avicennia marina) along the Arabian Gulf coast, Saudi Arabia
  8. Amino-functionalized graphene oxide for Cr(VI), Cu(II), Pb(II) and Cd(II) removal from industrial wastewater
  9. Chemical composition and in vitro activity of Origanum vulgare L., Satureja hortensis L., Thymus serpyllum L. and Thymus vulgaris L. essential oils towards oral isolates of Candida albicans and Candida glabrata
  10. Effect of excess Fluoride consumption on Urine-Serum Fluorides, Dental state and Thyroid Hormones among children in “Talab Sarai” Punjab Pakistan
  11. Design, Synthesis and Characterization of Novel Isoxazole Tagged Indole Hybrid Compounds
  12. Comparison of kinetic and enzymatic properties of intracellular phosphoserine aminotransferases from alkaliphilic and neutralophilic bacteria
  13. Green Organic Solvent-Free Oxidation of Alkylarenes with tert-Butyl Hydroperoxide Catalyzed by Water-Soluble Copper Complex
  14. Ducrosia ismaelis Asch. essential oil: chemical composition profile and anticancer, antimicrobial and antioxidant potential assessment
  15. DFT calculations as an efficient tool for prediction of Raman and infra-red spectra and activities of newly synthesized cathinones
  16. Influence of Chemical Osmosis on Solute Transport and Fluid Velocity in Clay Soils
  17. A New fatty acid and some triterpenoids from propolis of Nkambe (North-West Region, Cameroon) and evaluation of the antiradical scavenging activity of their extracts
  18. Antiplasmodial Activity of Stigmastane Steroids from Dryobalanops oblongifolia Stem Bark
  19. Rapid identification of direct-acting pancreatic protectants from Cyclocarya paliurus leaves tea by the method of serum pharmacochemistry combined with target cell extraction
  20. Immobilization of Pseudomonas aeruginosa static biomass on eggshell powder for on-line preconcentration and determination of Cr (VI)
  21. Assessment of methyl 2-({[(4,6-dimethoxypyrimidin-2-yl)carbamoyl] sulfamoyl}methyl)benzoate through biotic and abiotic degradation modes
  22. Stability of natural polyphenol fisetin in eye drops Stability of fisetin in eye drops
  23. Production of a bioflocculant by using activated sludge and its application in Pb(II) removal from aqueous solution
  24. Molecular Properties of Carbon Crystal Cubic Structures
  25. Synthesis and characterization of calcium carbonate whisker from yellow phosphorus slag
  26. Study on the interaction between catechin and cholesterol by the density functional theory
  27. Analysis of some pharmaceuticals in the presence of their synthetic impurities by applying hybrid micelle liquid chromatography
  28. Two mixed-ligand coordination polymers based on 2,5-thiophenedicarboxylic acid and flexible N-donor ligands: the protective effect on periodontitis via reducing the release of IL-1β and TNF-α
  29. Incorporation of silver stearate nanoparticles in methacrylate polymeric monoliths for hemeprotein isolation
  30. Development of ultrasound-assisted dispersive solid-phase microextraction based on mesoporous carbon coated with silica@iron oxide nanocomposite for preconcentration of Te and Tl in natural water systems
  31. N,N′-Bis[2-hydroxynaphthylidene]/[2-methoxybenzylidene]amino]oxamides and their divalent manganese complexes: Isolation, spectral characterization, morphology, antibacterial and cytotoxicity against leukemia cells
  32. Determination of the content of selected trace elements in Polish commercial fruit juices and health risk assessment
  33. Diorganotin(iv) benzyldithiocarbamate complexes: synthesis, characterization, and thermal and cytotoxicity study
  34. Keratin 17 is induced in prurigo nodularis lesions
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  36. LaCoO3 perovskite-type catalysts in syngas conversion
  37. Comparative studies of two vegetal extracts from Stokesia laevis and Geranium pratense: polyphenol profile, cytotoxic effect and antiproliferative activity
  38. Fragmentation pattern of certain isatin–indole antiproliferative conjugates with application to identify their in vitro metabolic profiles in rat liver microsomes by liquid chromatography tandem mass spectrometry
  39. Investigation of polyphenol profile, antioxidant activity and hepatoprotective potential of Aconogonon alpinum (All.) Schur roots
  40. Lead discovery of a guanidinyl tryptophan derivative on amyloid cascade inhibition
  41. Physicochemical evaluation of the fruit pulp of Opuntia spp growing in the Mediterranean area under hard climate conditions
  42. Electronic structural properties of amino/hydroxyl functionalized imidazolium-based bromide ionic liquids
  43. New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide and their Cu(ii), and Zn(ii) metal complexes: their in vitro antimicrobial potentials and in silico physicochemical and pharmacokinetics properties
  44. Treatment of adhesions after Achilles tendon injury using focused ultrasound with targeted bFGF plasmid-loaded cationic microbubbles
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  46. Chirality of β2-agonists. An overview of pharmacological activity, stereoselective analysis, and synthesis
  47. Fe3O4@urea/HITh-SO3H as an efficient and reusable catalyst for the solvent-free synthesis of 7-aryl-8H-benzo[h]indeno[1,2-b]quinoline-8-one and indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine derivatives
  48. Adsorption kinetic characteristics of molybdenum in yellow-brown soil in response to pH and phosphate
  49. Enhancement of thermal properties of bio-based microcapsules intended for textile applications
  50. Exploring the effect of khat (Catha edulis) chewing on the pharmacokinetics of the antiplatelet drug clopidogrel in rats using the newly developed LC-MS/MS technique
  51. A green strategy for obtaining anthraquinones from Rheum tanguticum by subcritical water
  52. Cadmium (Cd) chloride affects the nutrient uptake and Cd-resistant bacterium reduces the adsorption of Cd in muskmelon plants
  53. Removal of H2S by vermicompost biofilter and analysis on bacterial community
  54. Structural cytotoxicity relationship of 2-phenoxy(thiomethyl)pyridotriazolopyrimidines: Quantum chemical calculations and statistical analysis
  55. A self-breaking supramolecular plugging system as lost circulation material in oilfield
  56. Synthesis, characterization, and pharmacological evaluation of thiourea derivatives
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  58. Synthesis and characterization of a novel chitosan-grafted-polyorthoethylaniline biocomposite and utilization for dye removal from water
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  64. Study of the remediation effects of passivation materials on Pb-contaminated soil
  65. Saliva proteomic analysis reveals possible biomarkers of renal cell carcinoma
  66. Withania frutescens: Chemical characterization, analgesic, anti-inflammatory, and healing activities
  67. Design, synthesis and pharmacological profile of (−)-verbenone hydrazones
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  86. A promising naphthoquinone [8-hydroxy-2-(2-thienylcarbonyl)naphtho[2,3-b]thiophene-4,9-dione] exerts anti-colorectal cancer activity through ferroptosis and inhibition of MAPK signaling pathway based on RNA sequencing
  87. Synthesis and efficacy of herbicidal ionic liquids with chlorsulfuron as the anion
  88. Effect of isovalent substitution on the crystal structure and properties of two-slab indates BaLa2−xSmxIn2O7
  89. Synthesis, spectral and thermo-kinetics explorations of Schiff-base derived metal complexes
  90. An improved reduction method for phase stability testing in the single-phase region
  91. Comparative analysis of chemical composition of some commercially important fishes with an emphasis on various Malaysian diets
  92. Development of a solventless stir bar sorptive extraction/thermal desorption large volume injection capillary gas chromatographic-mass spectrometric method for ultra-trace determination of pyrethroids pesticides in river and tap water samples
  93. A turbidity sensor development based on NL-PI observers: Experimental application to the control of a Sinaloa’s River Spirulina maxima cultivation
  94. Deep desulfurization of sintering flue gas in iron and steel works based on low-temperature oxidation
  95. Investigations of metallic elements and phenolics in Chinese medicinal plants
  96. Influence of site-classification approach on geochemical background values
  97. Effects of ageing on the surface characteristics and Cu(ii) adsorption behaviour of rice husk biochar in soil
  98. Adsorption and sugarcane-bagasse-derived activated carbon-based mitigation of 1-[2-(2-chloroethoxy)phenyl]sulfonyl-3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl) urea-contaminated soils
  99. Antimicrobial and antifungal activities of bifunctional cooper(ii) complexes with non-steroidal anti-inflammatory drugs, flufenamic, mefenamic and tolfenamic acids and 1,10-phenanthroline
  100. Application of selenium and silicon to alleviate short-term drought stress in French marigold (Tagetes patula L.) as a model plant species
  101. Screening and analysis of xanthine oxidase inhibitors in jute leaves and their protective effects against hydrogen peroxide-induced oxidative stress in cells
  102. Synthesis and physicochemical studies of a series of mixed-ligand transition metal complexes and their molecular docking investigations against Coronavirus main protease
  103. A study of in vitro metabolism and cytotoxicity of mephedrone and methoxetamine in human and pig liver models using GC/MS and LC/MS analyses
  104. A new phenyl alkyl ester and a new combretin triterpene derivative from Combretum fragrans F. Hoffm (Combretaceae) and antiproliferative activity
  105. Erratum
  106. Erratum to: A one-step incubation ELISA kit for rapid determination of dibutyl phthalate in water, beverage and liquor
  107. Review Articles
  108. Sinoporphyrin sodium, a novel sensitizer for photodynamic and sonodynamic therapy
  109. Natural products isolated from Casimiroa
  110. Plant description, phytochemical constituents and bioactivities of Syzygium genus: A review
  111. Evaluation of elastomeric heat shielding materials as insulators for solid propellant rocket motors: A short review
  112. Special Issue on Applied Biochemistry and Biotechnology 2019
  113. An overview of Monascus fermentation processes for monacolin K production
  114. Study on online soft sensor method of total sugar content in chlorotetracycline fermentation tank
  115. Studies on the Anti-Gouty Arthritis and Anti-hyperuricemia Properties of Astilbin in Animal Models
  116. Effects of organic fertilizer on water use, photosynthetic characteristics, and fruit quality of pear jujube in northern Shaanxi
  117. Characteristics of the root exudate release system of typical plants in plateau lakeside wetland under phosphorus stress conditions
  118. Characterization of soil water by the means of hydrogen and oxygen isotope ratio at dry-wet season under different soil layers in the dry-hot valley of Jinsha River
  119. Composition and diurnal variation of floral scent emission in Rosa rugosa Thunb. and Tulipa gesneriana L.
  120. Preparation of a novel ginkgolide B niosomal composite drug
  121. The degradation, biodegradability and toxicity evaluation of sulfamethazine antibiotics by gamma radiation
  122. Special issue on Monitoring, Risk Assessment and Sustainable Management for the Exposure to Environmental Toxins
  123. Insight into the cadmium and zinc binding potential of humic acids derived from composts by EEM spectra combined with PARAFAC analysis
  124. Source apportionment of soil contamination based on multivariate receptor and robust geostatistics in a typical rural–urban area, Wuhan city, middle China
  125. Special Issue on 13th JCC 2018
  126. The Role of H2C2O4 and Na2CO3 as Precipitating Agents on The Physichochemical Properties and Photocatalytic Activity of Bismuth Oxide
  127. Preparation of magnetite-silica–cetyltrimethylammonium for phenol removal based on adsolubilization
  128. Topical Issue on Agriculture
  129. Size-dependent growth kinetics of struvite crystals in wastewater with calcium ions
  130. The effect of silica-calcite sedimentary rock contained in the chicken broiler diet on the overall quality of chicken muscles
  131. Physicochemical properties of selected herbicidal products containing nicosulfuron as an active ingredient
  132. Lycopene in tomatoes and tomato products
  133. Fluorescence in the assessment of the share of a key component in the mixing of feed
  134. Sulfur application alleviates chromium stress in maize and wheat
  135. Effectiveness of removal of sulphur compounds from the air after 3 years of biofiltration with a mixture of compost soil, peat, coconut fibre and oak bark
  136. Special Issue on the 4th Green Chemistry 2018
  137. Study and fire test of banana fibre reinforced composites with flame retardance properties
  138. Special Issue on the International conference CosCI 2018
  139. Disintegration, In vitro Dissolution, and Drug Release Kinetics Profiles of k-Carrageenan-based Nutraceutical Hard-shell Capsules Containing Salicylamide
  140. Synthesis of amorphous aluminosilicate from impure Indonesian kaolin
  141. Special Issue on the International Conf on Science, Applied Science, Teaching and Education 2019
  142. Functionalization of Congo red dye as a light harvester on solar cell
  143. The effect of nitrite food preservatives added to se’i meat on the expression of wild-type p53 protein
  144. Biocompatibility and osteoconductivity of scaffold porous composite collagen–hydroxyapatite based coral for bone regeneration
  145. Special Issue on the Joint Science Congress of Materials and Polymers (ISCMP 2019)
  146. Effect of natural boron mineral use on the essential oil ratio and components of Musk Sage (Salvia sclarea L.)
  147. A theoretical and experimental study of the adsorptive removal of hexavalent chromium ions using graphene oxide as an adsorbent
  148. A study on the bacterial adhesion of Streptococcus mutans in various dental ceramics: In vitro study
  149. Corrosion study of copper in aqueous sulfuric acid solution in the presence of (2E,5E)-2,5-dibenzylidenecyclopentanone and (2E,5E)-bis[(4-dimethylamino)benzylidene]cyclopentanone: Experimental and theoretical study
  150. Special Issue on Chemistry Today for Tomorrow 2019
  151. Diabetes mellitus type 2: Exploratory data analysis based on clinical reading
  152. Multivariate analysis for the classification of copper–lead and copper–zinc glasses
  153. Special Issue on Advances in Chemistry and Polymers
  154. The spatial and temporal distribution of cationic and anionic radicals in early embryo implantation
  155. Special Issue on 3rd IC3PE 2020
  156. Magnetic iron oxide/clay nanocomposites for adsorption and catalytic oxidation in water treatment applications
  157. Special Issue on IC3PE 2018/2019 Conference
  158. Exergy analysis of conventional and hydrothermal liquefaction–esterification processes of microalgae for biodiesel production
  159. Advancing biodiesel production from microalgae Spirulina sp. by a simultaneous extraction–transesterification process using palm oil as a co-solvent of methanol
  160. Topical Issue on Applications of Mathematics in Chemistry
  161. Omega and the related counting polynomials of some chemical structures
  162. M-polynomial and topological indices of zigzag edge coronoid fused by starphene
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