Serum bile acids profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and its application on pediatric liver and intestinal diseases
-
Xiaowei Fu
,
Yi Xiao
Abstract
Background
A method for bile acid profiling measuring 21 primary and secondary bile acids in serum samples was developed and validated with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sample preparation included spiking with internal standards followed by protein precipitation, centrifugation, drying under nitrogen gas and reconstitution. Extracted samples were injected onto a Phenomenex Kinetex C18 column (150 × 4.60 mm, 2.6 μm).
Methods
Data was collected with LC-MS/MS operated in negative ion mode with multiple reaction monitoring (MRM) and single reaction monitoring (SRM). The analytical run time was 12 min.
Results
The method showed excellent linearity with high regression coefficients (>0.99) over a range of 0.05 and 25 μM for all analytes tested. The method also showed acceptable intra-day and inter-day accuracy and precision. As a proof of concept, the analytical method was applied to patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), biliary atresia (BA), and necrotizing enterocolitis (NEC), and distinct bile acids profiles were demonstrated.
Conclusions
The method could be poised to identify possible biomarkers for non-invasive early diagnosis of these disorders.
Acknowledgments
The authors acknowledge the support of the staff in Biochemical Genetics and Special Chemistry at Children’s Hospital Los Angeles for analyzing the clinical samples in this report.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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©2020 Walter de Gruyter GmbH, Berlin/Boston
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- Editorial
- Advancements in mass spectrometry as a tool for clinical analysis: Part I
- Drug adherence, testing and therapeutic monitoring
- Hyphenated mass spectrometry techniques for assessing medication adherence: advantages, challenges, clinical applications and future perspectives
- Method development for quantitative determination of seven statins including four active metabolites by means of high-resolution tandem mass spectrometry applicable for adherence testing and therapeutic drug monitoring
- Validation of a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to detect cannabinoids in whole blood and breath
- THC and CBD concentrations in blood, oral fluid and urine following a single and repeated administration of “light cannabis”
- Identification of metabolites of peptide-derived drugs using an isotope-labeled reporter ion screening strategy
- Validation according to European and American regulatory agencies guidelines of an LC-MS/MS method for the quantification of free and total ropivacaine in human plasma
- Enhanced specificity due to method specific limits for relative ion intensities in a high-performance liquid chromatography – tandem mass spectrometry method for iohexol in human serum
- Small molecule biomarkers
- Applying mass spectrometry-based assays to explore gut microbial metabolism and associations with disease
- Trimethylamine-N-oxide (TMAO) determined by LC-MS/MS: distribution and correlates in the population-based PopGen cohort
- Development of a total serum testosterone, androstenedione, 17-hydroxyprogesterone, 11β-hydroxyandrostenedione and 11-ketotestosterone LC-MS/MS assay and its application to evaluate pre-analytical sample stability
- Short-term stability of free metanephrines in plasma and whole blood
- Validation of a rapid, comprehensive and clinically relevant amino acid profile by underivatised liquid chromatography tandem mass spectrometry
- UPLC-MS/MS method for determination of retinol and α-tocopherol in serum using a simple sample pretreatment and UniSpray as ionization technique to reduce matrix effects
- Independent association of plasma xanthine oxidoreductase activity with serum uric acid level based on stable isotope-labeled xanthine and liquid chromatography/triple quadrupole mass spectrometry: MedCity21 health examination registry
- Serum bile acids profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and its application on pediatric liver and intestinal diseases
- LC-MS/MS analysis of plasma glucosylsphingosine as a biomarker for diagnosis and follow-up monitoring in Gaucher disease in the Spanish population
- Dried blood spots and alternative sample mediums
- Investigating the suitability of high-resolution mass spectrometry for newborn screening: identification of hemoglobinopathies and β-thalassemias in dried blood spots
- Candidate reference method for determination of vitamin D from dried blood spot samples
- Therapeutic drug monitoring of anti-epileptic drugs – a clinical verification of volumetric absorptive micro sampling
- Simultaneous quantitation of five triazole anti-fungal agents by paper spray-mass spectrometry
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Articles in the same Issue
- Frontmatter
- Editorial
- Advancements in mass spectrometry as a tool for clinical analysis: Part I
- Drug adherence, testing and therapeutic monitoring
- Hyphenated mass spectrometry techniques for assessing medication adherence: advantages, challenges, clinical applications and future perspectives
- Method development for quantitative determination of seven statins including four active metabolites by means of high-resolution tandem mass spectrometry applicable for adherence testing and therapeutic drug monitoring
- Validation of a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to detect cannabinoids in whole blood and breath
- THC and CBD concentrations in blood, oral fluid and urine following a single and repeated administration of “light cannabis”
- Identification of metabolites of peptide-derived drugs using an isotope-labeled reporter ion screening strategy
- Validation according to European and American regulatory agencies guidelines of an LC-MS/MS method for the quantification of free and total ropivacaine in human plasma
- Enhanced specificity due to method specific limits for relative ion intensities in a high-performance liquid chromatography – tandem mass spectrometry method for iohexol in human serum
- Small molecule biomarkers
- Applying mass spectrometry-based assays to explore gut microbial metabolism and associations with disease
- Trimethylamine-N-oxide (TMAO) determined by LC-MS/MS: distribution and correlates in the population-based PopGen cohort
- Development of a total serum testosterone, androstenedione, 17-hydroxyprogesterone, 11β-hydroxyandrostenedione and 11-ketotestosterone LC-MS/MS assay and its application to evaluate pre-analytical sample stability
- Short-term stability of free metanephrines in plasma and whole blood
- Validation of a rapid, comprehensive and clinically relevant amino acid profile by underivatised liquid chromatography tandem mass spectrometry
- UPLC-MS/MS method for determination of retinol and α-tocopherol in serum using a simple sample pretreatment and UniSpray as ionization technique to reduce matrix effects
- Independent association of plasma xanthine oxidoreductase activity with serum uric acid level based on stable isotope-labeled xanthine and liquid chromatography/triple quadrupole mass spectrometry: MedCity21 health examination registry
- Serum bile acids profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and its application on pediatric liver and intestinal diseases
- LC-MS/MS analysis of plasma glucosylsphingosine as a biomarker for diagnosis and follow-up monitoring in Gaucher disease in the Spanish population
- Dried blood spots and alternative sample mediums
- Investigating the suitability of high-resolution mass spectrometry for newborn screening: identification of hemoglobinopathies and β-thalassemias in dried blood spots
- Candidate reference method for determination of vitamin D from dried blood spot samples
- Therapeutic drug monitoring of anti-epileptic drugs – a clinical verification of volumetric absorptive micro sampling
- Simultaneous quantitation of five triazole anti-fungal agents by paper spray-mass spectrometry
- Obtaining information from the brain in a non-invasive way: determination of iron in nasal exudate to differentiate hemorrhagic and ischemic strokes
