98%
921
2 minutes
20
Objective: The aim of this study is to develop a LC-MS/MS method for the quantitation of seven cytochrome P450 (CYP450) enzymes.
Methods: A high-performance liquid chromatography-tandem mass spectrometry method was developed using multiple reaction monitoring mode with positive electrospray ionization. The method was validated with selectivity, linearity, stability, accuracy and precious. In addition, the abundance of seven CYP450 enzymes in human liver microsomes and CYP3A4 in placenta were determined using the current method.
Results: The linear range for CYP1A2, CYP2B6 and CYP2C8 was 0.036-3.6 nM and for CYP2C9, CYP2C19, CYP2D6 and CYP3A4 was 0.090-9.0 nM. No interference was found between the blank matrix and each specific peptides. The accuracy and precious results were in accord with the requirement of analytical methods for biological samples in Chinese Pharmacopoeia. In addition, the peptides were stable under current stability conditions. The content of CYP3A4 in placenta and the seven CYP450 enzymes in human liver microsomes were accurately quantified.
Conclusion: The developed method is sensitive and specific and can be applied to the quantification of enzymes abundance in different human derived samples like placenta and liver microsomes.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.jchromb.2022.123536 | DOI Listing |
Drug Metab Dispos
July 2025
Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington; Division of Molecular Biosciences, Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York
Hydromorphone is a highly potent opioid used to treat severe chronic pain. It is metabolized primarily by UDP-glucuronosyltransferase (UGT)2B7 to form the inactive hydromorphone-3-glucuronide. Given that previous studies have shown that the major cannabinoids, Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD), inhibit several UGT enzymes, the objective of the present study was to determine the inhibitory potential of major cannabinoids and their metabolites on UGT-mediated hydromorphone metabolism.
View Article and Find Full Text PDFFront Vet Sci
August 2025
Guangdong Key Laboratory for Veterinary Drug Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Amphenmulin is a novel pleuromutilin derivative with proven excellent antibacterial activity. To investigate its metabolism in animals, ultra-high-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) was employed to analyze and identify metabolites in rats and chickens and using human, rat, pig, chicken and beagle dog liver microsomes. We identified 18 metabolites from liver microsomes and 24 and 17 metabolites for rats and chickens, respectively.
View Article and Find Full Text PDFAnal Methods
September 2025
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Avapritinib (Ayvakit™) is a highly selective inhibitor of the platelet-derived growth factor receptor alpha (PDGFRA), including D842V mutations. Avapritinib (APB) is authorized in the United States for individuals with metastatic or unresectable gastrointestinal stromal tumors (GISTs). APB is considered the exclusive therapy for adults with indolent systemic mastocytosis.
View Article and Find Full Text PDFBioorg Chem
September 2025
Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koam 32511, Egypt. Electronic address:
Targeting Cyclin-Dependent Kinase 2 (CDK2) remains a critical strategy in anticancer drug discovery. This study unveils a highly promising series of novel [1,2,4]triazolo[1,5-a]pyrimidine (TP) derivatives, achieved through innovative S/N-glycerolylation and peptide conjugation strategies. We report the rational design, efficient multi-step synthesis (yields up to 85 %), and comprehensive biological and computational evaluation.
View Article and Find Full Text PDFJ Cheminform
September 2025
College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.
The metabolic stability of a drug is a crucial determinant of its pharmacokinetic properties, including clearance, half-life, and oral bioavailability. Accurate predictions of metabolic stability can significantly streamline the drug discovery process. In this study, we present MetaboGNN, an advanced model for predicting liver metabolic stability based on Graph Neural Networks (GNNs) and Graph Contrastive Learning (GCL).
View Article and Find Full Text PDF