ArticleAnalytical chemistry2012
Quantification of human uridine-diphosphate glucuronosyl transferase 1A isoforms in liver, intestine, and kidney using nanobore liquid chromatography-tandem mass spectrometry.
Article in Analytical chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 171 citations in OpenAlex.
- Metabolism of Long-Acting Rilpivirine After Intramuscular Injection: HIV Prevention Trials Network Study 076 (HPTN 076).AIDS research and human retroviruses · 2021Trial
- Stereoselective Glucuronidation of Bupropion Metabolites In Vitro and In Vivo.Drug metabolism and disposition: the biological fate of chemicals · 2016Trial
- The influence of kidney function on dapagliflozin exposure, metabolism and pharmacodynamics in healthy subjects and in patients with type 2 diabetes mellitus.British journal of clinical pharmacology · 2013 · on this mapTrial
- Human and rat renal proximal tubule in vitro models for ADME applications.Archives of toxicology · 2025Review
- Matrix Approach Assessment of Cabotegravir Drug-Drug Interactions with OAT1/OAT3 Substrates and UGT1A1/UGT1A9 Inhibitors Using Physiologically-Based Pharmacokinetic Modeling.Pharmaceutics · 2025Article
- Development of a PBPK Model for Lamotrigine which Incorporates Metabolism by UGT2B10: Impact of UGT2B10 Poor Metabolizer Phenotype and Pregnancy.The AAPS journal · 2025Article
- Genome-wide analyses of neonatal jaundice reveal a marked departure from adult bilirubin metabolism.Nature communications · 2024Article
- Hepatic glucuronidation of tetrabromobisphenol A and tetrachlorobisphenol A: interspecies differences in humans and laboratory animals and responsible UDP-glucuronosyltransferase isoforms in humans.Archives of toxicology · 2024Article
- Data-independent acquisition (DIA): An emerging proteomics technology for analysis of drug-metabolizing enzymes and transporters.Drug discovery today. Technologies · 2021Review
- PBPK Modeling as a Tool for Predicting and Understanding Intestinal Metabolism of Uridine 5'-Diphospho-glucuronosyltransferase Substrates.Pharmaceutics · 2021Review
- Identification of Novel UGT1A1 Variants Including UGT1A1 454C>A through the Genotyping of Healthy Participants of the HPTN 077 Study.ACS pharmacology & translational science · 2021Article
- Case Study 6: Deconvoluting Hyperbilirubinemia-Differentiating Between Hepatotoxicity and Reversible Inhibition of UGT1A1, MRP2, or OATP1B1 in Drug Development.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Enzyme Kinetics of Uridine Diphosphate Glucuronosyltransferases (UGTs).Methods in molecular biology (Clifton, N.J.) · 2021Article
- Investigation on the metabolic characteristics of isobavachin in Psoralea corylifolia L. (Bu-gu-zhi) and its potential inhibition against human cytochrome P450s and UDP-glucuronosyltransferases.The Journal of pharmacy and pharmacology · 2020Article
- In Vitro to In Vivo Extrapolation of Metabolic Clearance for UGT Substrates Using Short-Term Suspension and Long-Term Co-cultured Human Hepatocytes.The AAPS journal · 2020Article
- Construction and Verification of Physiologically Based Pharmacokinetic Models for Four Drugs Majorly Cleared by Glucuronidation: Lorazepam, Oxazepam, Naloxone, and Zidovudine.The AAPS journal · 2020Article
- Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters.Molecules (Basel, Switzerland) · 2020Review
- Quantitative Proteomics of Clinically Relevant Drug-Metabolizing Enzymes and Drug Transporters and Their Intercorrelations in the Human Small Intestine.Drug metabolism and disposition: the biological fate of chemicals · 2020Observational
- Label-free absolute protein quantification with data-independent acquisition.Journal of proteomics · 2019Article
- The Ontogeny of UDP-glucuronosyltransferase Enzymes, Recommendations for Future Profiling Studies and Application Through Physiologically Based Pharmacokinetic Modelling.Clinical pharmacokinetics · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Uridine-disphosphate glucuronosyl transferase (UGT) enzymes catalyze the formation of glucuronide conjugates of phase II metabolism. Methods for absolute quantification of UGT1A1 and UGT1A6 were previously established utilizing stable isotope peptide internal standards with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The current method expands upon this by quantifying eight UGT1A isoforms by nanobore high-performance liquid chromatography (HPLC) coupled with a linear ion trap time-of-flight mass spectrometer platform. Recombinant enzyme digests of each of the isoforms were used to determine assay linearity and detection limits. Enzyme expression level in human liver, kidney, and intestinal microsomal protein was determined by extrapolation from spiked stable isotope standards. Intraday and interday variability was <25% for each of the enzyme isoforms. Enzyme expression varied from 3 to 96 pmol/mg protein in liver and intestinal microsomal protein digests. Expression levels of UGT1A7, 1A8, and 1A10 were below detection limits (<1 pmol/mg protein) in human liver microsome (HLMs). In kidney microsomes the expression of UGT1A3 was below detection limits, but levels of UGT1A4, 1A7, 1A9, and 1A10 protein were higher relative to that of liver, suggesting that renal glucuronidation could be a significant factor in renal elimination of glucuronide conjugates. This novel method allows quantification of all nine UGT1A isoforms, many previously not amenable to measurement with traditional methods such as immunologically based assays. Quantitative measurement of proteins involved in drug disposition, such as the UGTs, significantly improves the ability to evaluate and interpret in vitro and in vivo studies in drug development.
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