Moon, Ju-Yeon Kang, Se Mi Lee, Jeongae Cho, Joo-Youn Moon, Myeong Hee Jang, In-Jin Chung, Bong Chul Choi, Man Ho 2024-01-20T12:00:53Z 2024-01-20T12:00:53Z 2021-09-05 2013-08 0163-4356 https://pubs.kist.re.kr/handle/201004/127818 Background: Drug-induced cytochrome P450 (CYP) activity affects endocrine function and drug clearance rates, leading to the development of unpredictable pathologic and toxicologic risks.Methods: Urinary steroid profiling based on gas chromatography-mass spectrometry (GC-MS) was used for simultaneous quantification of CYP-mediated regioselective hydroxysteroids and their substrates, including 26 androgens, 9 estrogens, 5 progestins, and 7 corticoids. The quantitative data were visualized using a hierarchically clustered heat map to allow identification of CYP-mediated steroid signatures. Twelve healthy subjects were orally administered 600 mg of rifampicin a day for 7 days, and their CYP enzyme activity was evaluated.Results: Using GC-MS, all 47 steroids were well separated with good peak shapes. This assay had good linearity (r(2) > 0.994) in a dynamic range, and the interassay imprecision (% CV) and inaccuracy (% bias) were 3.0%-15.6% and 98.0%-109.2%, respectively. Administration of the CYP3A4 inducer rifampicin produced distinct differences in CYP3A4 and CYP11B1, CYP19A1, HSD11B, and HSD17B, which were indicated by their heat map-visualized steroid signatures.Conclusions: This CYP-mediated steroid signature profile allows simultaneous assessment of CYP1A, CYP1B, CYP2C, CYP3A, CYP11B, CYP17A, CYP19A, and CYP21A in urine samples. This method could therefore be a useful tool for assessing drug efficacy. English LIPPINCOTT WILLIAMS & WILKINS PREGNANE-X-RECEPTOR MASS-SPECTROMETRY URINARY 6-BETA-HYDROXYCORTISOL POSTMENOPAUSAL WOMEN METABOLISM HYDROXYLATION TESTOSTERONE ASSAYS CYP3A 4-HYDROXYANDROSTENEDIONE GC-MS-Based Quantitative Signatures of Cytochrome P450-Mediated Steroid Oxidation Induced by Rifampicin Article 10.1097/FTD.0b013e318286ee02 1 THERAPEUTIC DRUG MONITORING, v.35, no.4, pp.473 - 484 THERAPEUTIC DRUG MONITORING 35 4 473 484 scie scopus 000322202600007 2-s2.0-84880570391 Medical Laboratory Technology Pharmacology & Pharmacy Toxicology Medical Laboratory Technology Pharmacology & Pharmacy Toxicology Article PREGNANE-X-RECEPTOR MASS-SPECTROMETRY URINARY 6-BETA-HYDROXYCORTISOL POSTMENOPAUSAL WOMEN METABOLISM HYDROXYLATION TESTOSTERONE ASSAYS CYP3A 4-HYDROXYANDROSTENEDIONE cytochrome P450 steroid hydroxylation GC-MS steroid signatures rifampicin