Quantitative determination of D4-cystine in mice using LC-MS/MS and its application to the assessment of pharmacokinetics and bioavailability / 药物分析学报
Journal of Pharmaceutical Analysis
;
(6): 580-587, 2021.
Article
in Chinese
| WPRIM
| ID: wpr-908777
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Language:
Chinese
Journal:
Journal of Pharmaceutical Analysis
Year:
2021
Type:
Article
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