Quantification of vancomycin in human serum by LC-MS/MS
-
Katrin König
,
Uwe Kobold
Abstract
Background: The aim of our work was to develop and validate a reliable LC-MS/MS-based measurement procedure for the quantification of vancomycin in serum, to be applied in the context of efforts to standardize and harmonize therapeutic drug monitoring of this compound using routine assays.
Methods: Sample preparation was based on protein precipitation followed by ultrafiltration. In order to minimize differential modulation of ionization by matrix constituents extended chromatographic separation was applied leading to a retention time of 9.8 min for the analyte. Measurement was done by HPLC-ESI-MS/MS. For internal standardization the derivative vancomycin-glycin (ISTD) prepared by chemical synthesis was used, HPLC conditions ensured coelution of ISTD with the analyte.
Results: In a bi-center validation total CVs of <4% were observed for quality control material ranging from 5.3 mg/L to 79.4 mg/L; accuracy was ±4%. No relevant ion suppression was observed. Comparative measurement of aliquots from 70 samples at the two validation sites demonstrated close agreement.
Conclusions: Employing a closely related homologue molecule for internal standardization and the use of MS/MS following highly efficient sample pre-fractionation by HPLC, the method described here can be considered to offer the highest level of analytical reliability realized so far for the quantification of vancomycin in human serum. Thus, the method is suitable to be used in a comprehensive reference measurement system for vancomycin.
We thank the Referenzinstitut für Bioanalytik (RfB) for the permission to report the results of a vancomycin proficiency testing program.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
References
1. Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr., Craig W, Billeter M, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health-Syst Pharm 2009;66:82–98.10.2146/ajhp080434Suche in Google Scholar
2. Roberts JA, Norris R, Paterson DL, Martin JH. Therapeutic drug monitoring of antimicrobials. Br J Clin Pharmacol 2012;73:27–36.10.1111/j.1365-2125.2011.04080.xSuche in Google Scholar
3. Moise-Broder PA, Forrest A, Birmingham MC, Schentag JJ. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet 2004;43:925–42.10.2165/00003088-200443130-00005Suche in Google Scholar
4. Cano EL, Haque NZ, Welch VL, Cely CM, Peyrani P, Scerpella EG, et al. Incidence of nephrotoxicity and association with vancomycin use in intensive care unit patients with pneumonia: retrospective analysis of the IMPACT-HAP Database. Clin Ther 2012;34:149–57.10.1016/j.clinthera.2011.12.013Suche in Google Scholar
5. Wong-Beringer A, Joo J, Tse E, Beringer P. Vancomycin-associated nephrotoxicity: a critical appraisal of risk with high-dose therapy. Int J Antimicrob Agents 2011;37:95–101.10.1016/j.ijantimicag.2010.10.013Suche in Google Scholar
6. Wilson JF, Davis AC, Tobin CM. Evaluation of commercial assays for vancomycin and aminoglycosides in serum: a comparison of accuracy and precision based on external quality assessment. J Antimicrob Chemother 2003;52:78–82.10.1093/jac/dkg296Suche in Google Scholar
7. Cass RT, Villa JS, Karr DE, Schmidt DE Jr. Rapid bioanalysis of vancomycin in serum and urine by high-performance liquid chromatography tandem mass spectrometry using on-line sample extraction and parallel analytical columns. Rapid Commun Mass Spectrom 2001;15:406–12.10.1002/rcm.246Suche in Google Scholar
8. Zhang T, Watson DG, Azike C, Tettey JN, Stearns AT, Binning AR, et al. Determination of vancomycin in serum by liquid chromatography-high resolution full scan mass spectrometry. J Chromatogr B 2007;857:352–6.10.1016/j.jchromb.2007.07.041Suche in Google Scholar
9. Shibata N, Ishida M, Prasad YV, Gao W, Yoshikawa Y, Takada K. Highly sensitive quantification of vancomycin in plasma samples using liquid chromatography-tandem mass spectrometry and oral bioavailability in rats. J Chromatogr B 2003;789:211–8.10.1016/S1570-0232(03)00068-0Suche in Google Scholar
10. Stepman HC, Vanderroost A, Van Uytfanghe K, Thienpont LM. Candidate reference measurement procedures for serum 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 by using isotope-dilution liquid chromatography-tandem mass spectrometry. Clin Chem 2011;57:441–8.10.1373/clinchem.2010.152553Suche in Google Scholar PubMed
11. Annesley TM. Ion suppression in mass spectrometry. Clin Chem 2003;49:1041–4.10.1373/49.7.1041Suche in Google Scholar PubMed
12. Matuszewski BK, Constanzer ML, Chavez-Eng CM. Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS. Anal Chem 2003;75:3019–30.10.1021/ac020361sSuche in Google Scholar PubMed
13. Guidance for Industry-Bioanalytical Method Validation. U.S. Department of Health and Human Services-Food and Drug Administration; 2001. Available from: http://www.fda.gov/downloads/Drugs/…/Guidances/ucm070107.pdf. Accessed on February, 2012.Suche in Google Scholar
©2013 by Walter de Gruyter Berlin Boston
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