GC-MS-based quantitative signatures of cytochrome P450-mediated steroid oxidation induced by rifampicin

Ju Yeon Moon, Se Mi Kang, Jeongae Lee, Joo Youn Cho, Myeong Hee Moon, In Jin Jang, Bong Chul Chung, Man Ho Choi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 > 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.

Original languageEnglish
Pages (from-to)473-484
Number of pages12
JournalTherapeutic Drug Monitoring
Volume35
Issue number4
DOIs
Publication statusPublished - 2013 Aug 1

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Rifampin
Gas Chromatography-Mass Spectrometry
Cytochrome P-450 Enzyme System
Steroids
Cytochrome P-450 CYP3A
Steroid 11-beta-Hydroxylase
Hot Temperature
Pharmaceutical Preparations
Hydroxysteroids
Progestins
Androgens
Healthy Volunteers
Adrenal Cortex Hormones
Estrogens
Urine

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Moon, Ju Yeon ; Kang, Se Mi ; Lee, Jeongae ; Cho, Joo Youn ; Moon, Myeong Hee ; Jang, In Jin ; Chung, Bong Chul ; Choi, Man Ho. / GC-MS-based quantitative signatures of cytochrome P450-mediated steroid oxidation induced by rifampicin. In: Therapeutic Drug Monitoring. 2013 ; Vol. 35, No. 4. pp. 473-484.
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abstract = "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 > 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.",
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GC-MS-based quantitative signatures of cytochrome P450-mediated steroid oxidation induced by rifampicin. / Moon, Ju Yeon; Kang, Se Mi; Lee, Jeongae; Cho, Joo Youn; Moon, Myeong Hee; Jang, In Jin; Chung, Bong Chul; Choi, Man Ho.

In: Therapeutic Drug Monitoring, Vol. 35, No. 4, 01.08.2013, p. 473-484.

Research output: Contribution to journalArticle

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AU - Moon, Ju Yeon

AU - Kang, Se Mi

AU - Lee, Jeongae

AU - Cho, Joo Youn

AU - Moon, Myeong Hee

AU - Jang, In Jin

AU - Chung, Bong Chul

AU - Choi, Man Ho

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N2 - 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 > 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.

AB - 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 > 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.

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