当前位置: X-MOL 学术J. Pharm. Anal. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Quantitative determination of D4-cystine in mice using LC-MS/MS and its application to the assessment of pharmacokinetics and bioavailability
Journal of Pharmaceutical Analysis ( IF 8.8 ) Pub Date : 2020-09-12 , DOI: 10.1016/j.jpha.2020.08.010
Shuning Li 1 , Zhenyao Lu 1 , Li Jiao 1 , Ran Zhang 1 , Yu Hong 1 , Jiye Aa 1 , Guangji Wang 1
Affiliation  

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.



中文翻译:

使用 LC-MS/MS 定量测定小鼠中的 D4-胱氨酸及其在药代动力学和生物利用度评估中的应用

胱氨酸是合成谷胱甘肽的主要原料。然而,胱氨酸的药代动力学和组织分布在很大程度上是未知的。采用替代分析物 D 4 -胱氨酸生成校准曲线,用于通过液相色谱-串联质谱 (LC-MS/MS) 测定小鼠中 D 4 -胱氨酸和内源性胱氨酸的水平。验证评估证明了该方法的灵敏度、特异性和重现性,血浆中 5–5000 ng/mL 的定量下限 (LLOQ) 为 5 ng/mL。D 4的药代动力学在注射和口服溶液后评估 -胱氨酸,这两种方法对内源性胱氨酸水平的影响最小。在剂量为 25、50 和 100 mg/kg 时,胱氨酸的绝对生物利用度分别为 18.6%、15.1% 和 25.6%。静脉注射 D 4 -胱氨酸导致血浆水平显着升高,脑和肝脏中的水平降低。胃内施用的 D 4 -胱氨酸导致血浆和胃中的高水平,而肺、肾、心脏和脑中的水平相对较低。

更新日期:2020-09-12
down
wechat
bug