用于测定小鼠、大鼠、犬和仓鼠血液中DNDI-VL-2098的液相色谱-串联质谱法的开发与验证
Development and validation of LC-MS/MS method for determination of DNDI-VL-2098 in mouse, rat, dog and hamster blood.
作者信息
Patel Bhavesh D, Uppal Ritika, Pulakundam Nageswararao, Patel Jignesh P, Ramanathan Vikram, Ameta Rakshit, Launay Delphine, Braillard Stéphanie
机构信息
Drug Metabolism Pharmacokinetics & Bioanalysis, Eurofins Advinus Ltd, 21 & 22, Phase II, Peenya Industrial Area, Bengaluru 560058, India.
Department of Chemistry, PAHER University, Udaipur 313003, Rajasthan, India.
出版信息
Bioanalysis. 2019 Aug;11(15):1419-1435. doi: 10.4155/bio-2019-0128.
To develop a bioanalytical method to support pharmacokinetic evaluation of DNDI-VL-2098 in mouse, rat, dog and hamster following oral administration. A robust LC-MS/MS bioanalytical method was developed to quantify DNDI-VL-2098. DNDI-VL-2098 showed time-dependent recovery loss in acetonitrile precipitated plasma in all species. Acid-lysed whole blood was identified as a matrix in which recovery was stable over time. A two-step extraction procedure was used, with protein precipitation followed by liquid-liquid extraction with methyl tert-butyl ether. The assay was validated in the dynamic range of 5-5000 ng/ml for mouse, rat and dog blood, and a fit-for-purpose method was developed for hamster. A specific LC-MS/MS assay for DNDI-VL-2098 was developed and validated in hemolyzed blood.
开发一种生物分析方法，以支持DNDI-VL-2098在小鼠、大鼠、犬和仓鼠口服给药后的药代动力学评估。建立了一种稳健的液相色谱-串联质谱（LC-MS/MS）生物分析方法来定量DNDI-VL-2098。在所有物种中，DNDI-VL-2098在乙腈沉淀血浆中显示出随时间的回收率损失。酸裂解全血被确定为回收率随时间稳定的基质。采用两步萃取程序，先进行蛋白沉淀，然后用甲基叔丁基醚进行液-液萃取。该测定法在小鼠、大鼠和犬血5-5000 ng/ml的动态范围内得到验证，并为仓鼠开发了一种适用的方法。开发了一种针对DNDI-VL-2098的特异性LC-MS/MS测定法，并在溶血血液中进行了验证。
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