Dittakavi Sreekanth, Jat Rakesh Kumar, Mullangi Ramesh
Drug Metabolism and Pharmacokinetics, Jubilant Biosys, Yeshwanthpur, Bangalore, India.
Principal and Professor, Head of Institute of Pharmacy, Shri Jagdish Prasad Jhabarmal Tibrewala University, Jhunjhunu, Rajasthan, India.
Drug Res (Stuttg). 2019 Sep;69(9):505-511. doi: 10.1055/a-0857-6591. Epub 2019 Mar 1.
Ivosidenib is an approved drug for relapsed or refractory IDH1 mutant AML patients. The goal of the present work is to develop and validate an LC-MS/MS method for the quantitation of ivosidenib in mice dried blood spots (DBS) as per regulatory guideline in the linearity range of 1.10-3293 ng/mL. To date there is no bioanalytical method reported for quantitation of ivosidenib. The chromatographic resolution of ivosidenib and internal standard (warfarin) was achieved on a C column with an isocratic mobile phase. All validation parameters met the acceptance criteria. The intra- and inter-day precision was in the range of 2.79-10.5 and 5.76-9.02%, respectively. Ivosidenib was stable for 3 freeze/thaw cycles, up to 7 days at room temperature and for one month at -80°C. The applicability of the validated method is shown in a mice pharmacokinetic study. Ivosidenib was quantifiable up to 24 and 36 h following intravenous and oral administration to mice, respectively. The oral bioavailability was 48%. Comparison of DBS vs. plasma concentrations of ivosidenib showed excellent correlation, indicating DBS can be used as an alternative for plasma for pharmacokinetic analysis.
艾伏尼布是一种已获批用于复发或难治性异柠檬酸脱氢酶-1（IDH1）突变型急性髓系白血病（AML）患者的药物。本研究的目的是根据监管指南，开发并验证一种液相色谱-串联质谱（LC-MS/MS）方法，用于定量测定小鼠干血斑（DBS）中艾伏尼布的含量，线性范围为1.10 - 3293 ng/mL。迄今为止，尚未有报道用于定量艾伏尼布的生物分析方法。艾伏尼布和内标（华法林）在C柱上采用等度流动相实现了色谱分离。所有验证参数均符合验收标准。日内和日间精密度分别在2.79 - 10.5%和5.76 - 9.02%范围内。艾伏尼布在3次冻融循环中稳定，在室温下可稳定7天，在-80°C下可稳定1个月。在一项小鼠药代动力学研究中展示了该验证方法的适用性。分别对小鼠静脉注射和口服给药后，艾伏尼布在24小时和36小时内均可定量。口服生物利用度为48%。艾伏尼布的DBS浓度与血浆浓度比较显示出极好的相关性，表明DBS可作为血浆的替代物用于药代动力学分析。
