PT  - JOURNAL ARTICLE
AU  - Jiamei Chen
AU  - Lijun Zhu
AU  - Xiaoyan Li
AU  - Haihui Zheng
AU  - Tongmeng Yan
AU  - Cong Xie
AU  - Sijing Zeng
AU  - Jia Yu
AU  - Huangyu Jiang
AU  - Linlin Lu
AU  - Xiaoxiao Qi
AU  - Ying Wang
AU  - Ming Hu
AU  - Zhongqiu Liu
TI  - High Throughput and Reliable Isotope Label-free approach for Profiling 24 Metabolic Enzymes in FVB Mice and Gender Differences
AID  - 10.1124/dmd.116.074682
DP  - 2017 Jan 01
TA  - Drug Metabolism and Disposition
PG  - dmd.116.074682
4099  - http://dmd.aspetjournals.org/content/early/2017/03/29/dmd.116.074682.short
4100  - http://dmd.aspetjournals.org/content/early/2017/03/29/dmd.116.074682.full
AB  - FVB mice are extensively used in transgenic and pharmacokinetic research. In this study, a validated isotope label-free method of using ultrahigh-performance liquid chromatography (UHPLC)-MS/MS was established for quantifying 24 drug-metabolizing enzymes (DMEs) in FVB mice. The DMEs include cytochrome P450 (CYPs/Cyps), UDP-glucuronsyltransferases (UGTs/Ugts), and sulfotransferases (SULTs/Sults), which are the major phase I and II metabolic enzymes responsible for clearing and detoxifying xenobiotic and endogenous substances. The proposed UHPLC-MS/MS method displayed excellent dynamic range and high sensitivity for signature peptides, as well as acceptable recovery, accuracy and precision. The protein expression profiles of the DMEs were determined in male and female mice. Overall, major Cyps, Ugts, and Sults were expressed in male mice in the following rank-order: Cyp2c29 > 2e1 > 3a11 > 1a2 > 2d22 > 27a1 > 2c39; Ugt2b5 > 2b1 > 1a6a > 1a9 > 1a1 > 2a3 > 1a2 > 1a5; and Sult1a1 > 3a > 1d1. Whereas, in female mice, Cyp2c29 > 2e1 > 2c39 > 2d22 > 3a11 > 1a2 > 27a1; Ugt1a6a > 2b5 > 1a1 > 2b1 > 2a3 > 1a9 > 1a5 > 1a2; and Sult1a1 > 3a1 > 1d1. Cyp2c29, Cyp1a2, Cyp27a1, Ugt2b1, Ugt2b5 and Ugt2b36 were male-predominant. Cyp2c39, Cyp2d22, Cyp7a1, Ugt1a1, Ugt1a5, Sult1a1, Sult3a1, and Sult1d1 were female-predominant. This work could serve as a useful reference for the metabolic study of new drugs and for elucidating the effectiveness and toxicity of drugs. The method is a stable, simple, and rapid for determining the expression of DMEs in animals.