Quantitative determination of D_(4)-cystine in mice using LC-MS/MS and its application to the assessment of pharmacokinetics and bioavailability  

作　　者：Shuning Li Zhenyao Lu Li Jiao Ran Zhang Yu Hong Jiye Aa Guangji Wang 

机构地区：[1]Jiangsu Province Key Laboratory of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing,Jiangsu,210009,China

出　　处：《Journal of Pharmaceutical Analysis》2021年第5期580-587,共8页药物分析学报（英文版）

基　　金：This study was financially supported by the National Natural Science Foundation of the People's Republic of China(Grant Nos.:81773814 and 81530098);the National Key Special Project of Science and Technology for Innovation Drugs of China(Project No.:2017ZX09301013);the National Key Research and Development Program(Grant No.:2018YFC0807403).

摘　　要：Cystine is the primary source material for the synthesis of glutathione.However,the pharmacokinetics and tissue distribution of cystine are largely unknown.A surrogate analyte D_(4)-cystine was employed to generate calibration curves for the determination of levels of D_(4)-cystine and endogenous cystine in mice by liquid chromatography-tandem mass spectrometry(LC-MS/MS).Validation assessments proved the sensitivity,specificity and reproducibility of the method with a lower limit of quantification(LLOQ)of 5 ng/mL over 5e5000 ng/mL in plasma.The pharmacokinetics of D_(4)-cystine were evaluated after administering injections and oral solutions,both of which minimally impacted endogenous cystine levels.The absolute bioavailability of cystine was 18.6%,15.1%and 25.6%at doses of 25,50 and 100 mg/kg,respectively.Intravenously injected D_(4)-cystine resulted in dramatically high plasma levels with reduced levels in the brain and liver.Intragastrically administered D_(4)-cystine resulted in high levels in the plasma and stomach with relatively low levels in the lung,kidney,heart and brain.

关 键 词：CYSTINE LC-MS/MS PHARMACOKINETICS DISTRIBUTION Absolute bioavailability 

分 类 号：R965[医药卫生—药理学]