Patel Bhavesh D, Uppal Ritika, Pulakundam Nageswararao, Patel Jignesh P, Ramanathan Vikram, Ameta Rakshit, Launay Delphine, Braillard Stéphanie
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.
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。
