Development of Caffeine Metabolite Analysis Method for Evaluation of Various Drug Metabolic Enzyme Phenotype

Title
Development of Caffeine Metabolite Analysis Method for Evaluation of Various Drug Metabolic Enzyme Phenotype
Other Titles
카페인 대사체를 이용한 다종의 약물대사효소 기능 평가 연구
Author
Kim, Hyeong Jun
Alternative Author(s)
김형준
Advisor(s)
유혜현
Issue Date
2018-02
Publisher
한양대학교
Degree
Master
Abstract
The caffeine metabolic ratio, in urine, plasma or saliva, has been used extensively as an index of CYP1A2, NAT2, XO and CYP2A6 enzymatic activities. Based on existing study, we have developed and validated a high performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for determining urine caffeine and 14 caffeine metabolites suitable for estimating caffeine exposure and metabolic enzyme phenotyping studies. Collected urine samples were diluted with distilled water and cleaned upon Sep-Pak C18 cartridges. Limits of detection were 0.01–25 µg/mL depending on the analytes. Method imprecision, based on total coefficients of variation, was generally <15 % which is suitable for FDA guide for validation. Recoveries of all analytes were typically within 15 % of being quantitative (100 %) and all compounds were stable in test condition except for AAMU and AFMU at long-term stability (within 15% variation). We applied this method to the analysis of a conventional set of human urine samples and were able to detect a majority of the analytes in ≥99 % of samples as well as calculate caffeine metabolite phenotyping ratios for CYP1A2, NAT2, XO, and CYP2A6. Our study can provide the rapid, sensitive, accurate, precise, and simultaneous measurement of urine caffeine and caffeine metabolites. Futhermore, phenotyping with the assistance of caffeine as a probe substrate may provide useful assessment of CYP1A2, NAT2, XO and CYP2A6 activities in epidemiologic and drug-drug interaction studies.
URI
http://www.dcollection.net/handler/hanyang/000000105744http://repository.hanyang.ac.kr/handle/20.500.11754/68268
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > PHARMACY(약학과) > Theses (Master)
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