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目的建立测定富马酸替诺福韦酯中杂质9-丙烯基腺嘌呤含量的LC-MS/MS法。方法采用Thermo BDS(100 mm×4.6 mm,2.4μm)色谱柱,以甲醇-水(体积比为60∶40)为流动相,流速为0.3 m L·min~(-1)。选用ESI源以多反应监测(MRM)方式进行正离子检测,用于定量分析的离子反应为m/z 176.2→m/z 136.3。结果 9-丙烯基腺嘌呤在0.20~20μg·L~(-1)内线性关系良好,定量限为0.20μg·L~(-1),日内、日间精密度(RSD)均小于11.4%,准确度(RE)在3.7%以内,平均加样回收率为103%(n=6)。结论应用此方法测定了3批原料药中杂质9-丙烯基腺嘌呤的含量,结果均满足世界卫生组织(WHO)对其限量(不超过5 mg·L~(-1))检查的要求。
OBJECTIVE To establish an LC-MS / MS method for the determination of 9-propenyl adenine impurity in tenofovir disoproxil fumarate. Methods A Thermo BDS (100 mm × 4.6 mm, 2.4 μm) column was used. The mobile phase was methanol - water (60:40 by volume) at a flow rate of 0.3 m L · min -1. The ESI source was used for positive ion detection by MRM. The ion reaction for quantitative analysis was m / z 176.2 → m / z 136.3. Results The linearity of 9-propenyladenine was 0.20 ~ 20μg · L -1 with a limit of quantification of 0.20μg · L -1. The intra-day and inter-day precision was less than 11.4% The accuracy (RE) was within 3.7% and the average recovery was 103% (n = 6). Conclusions This method was used to determine the content of 9-propenyladenine in all three batches of raw materials. The results meet the requirements of the World Health Organization (WHO) for its limit test (not exceeding 5 mg · L -1).