Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), National drug clinical trial center, Peking University Cancer Hospital & Institute, Beijing, P. R. China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, P. R. China.
J Sep Sci. 2021 Mar;44(5):945-953. doi: 10.1002/jssc.202001023. Epub 2021 Jan 18.
TQ-B3203 is a new topoisomerase I inhibitor derived from camptothecin. In this paper, a simple and reliable ultra high-performance liquid chromatography-tandem mass spectrometric method was developed and validated for determination of TQ-B3203 in human plasma with TQ-B3203-d used as the internal standard. Bis(p-nitrophenyl)phosphate (2 mol/L) was added to ensure the stability of TQ-B3203 in human plasma. Plasma samples were protein precipitated by methanol and processed samples were chromatographed on an AQUITY BEH C column (50 × 2.1 mm, id 1.7 μm) with acetonitrile and water (0.1% formic acid) as the mobile phase. The calibration curves showed good linearity (R≥0.99) over the concentration range of 0.5-500 ng/mL. Within- and between-run precision were ≤5.8% and the accuracy was within the range of -8.3 to 14.0%. This method was further successfully applied to a pharmacokinetic study of TQ-B3203 in Chinese advanced solid cancer patients after administration of TQ-B3203 liposome injection.
TQ-B3203 是一种新型拓扑异构酶 I 抑制剂，来源于喜树碱。本文建立并验证了一种简单可靠的超高效液相色谱-串联质谱法，用于测定人血浆中的 TQ-B3203，以 TQ-B3203-d 作为内标。为了确保 TQ-B3203 在人血浆中的稳定性，加入了双（对硝基苯基）磷酸酯（2 mol/L）。采用甲醇沉淀蛋白，处理后的样品在 AQUITY BEH C 柱（50×2.1mm，id 1.7μm）上进行色谱分离，以乙腈和水（0.1%甲酸）为流动相。校准曲线在 0.5-500ng/mL 浓度范围内具有良好的线性（R≥0.99）。日内和日间精密度均≤5.8%，准确度在-8.3%至 14.0%范围内。该方法进一步成功应用于 TQ-B3203 脂质体注射液给药后中国晚期实体瘤患者的 TQ-B3203 药代动力学研究。
