Quantitative determination of D4-cystine in mice using LC-MS/MS and its application to the assessment of pharmacokinetics and bioavailability
- Author:
Li SHUNING
1
;
Lu ZHENYAO
;
Jiao LI
;
Zhang RAN
;
Hong YU
;
Aa JIYE
;
Wang GUANGJI
Author Information
1. Jiangsu Province Key Laboratory of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing,Jiangsu,210009,China
- Keywords:
Cystine;
LC-MS/MS;
Pharmacokinetics;
Distribution;
Absolute bioavailability
- From:
Journal of Pharmaceutical Analysis
2021;11(5):580-587
- CountryChina
- Language:Chinese
-
Abstract:
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 D4-cystine was employed to generate calibration curves for the determination of levels of D4-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 5-5000 ng/mL in plasma.The pharmacokinetics of D4-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 D4-cystine resulted in dramatically high plasma levels with reduced levels in the brain and liver.Intragastrically administered D4-cystine resulted in high levels in the plasma and stomach with relatively low levels in the lung,kidney,heart and brain.
