LC-MS/MS法联合ICP-MS法测定非小细胞肺癌患者血浆培美曲塞及顺铂的浓度

目的: 分别采用液-质联用和电感耦合等离子体质谱测定人血浆中培美曲塞和顺铂的浓度,为培美曲塞和顺铂的人体药动学研究提供数据支持。方法: 对于培美曲塞,采用ACE C₁₈(50.0 mm×2.1 mm,5.0 μm)色谱柱,以含0.2%甲酸的水溶液和含0.2%甲酸的乙腈为流动相,梯度洗脱2.9 min,进样体积20.0 μL,采用电喷雾离子化源,正离子模式,多反应监测扫描方式进行监测,离子反应对分别为m/z 428.2→163.1(培美曲塞)和m/z 433.2→163.1(培美曲塞-d5)。对于顺铂,设置质谱蠕动泵速度为40.0 r·min^-1,等离子体功率1 150.0 W,样本深度5.0 mm,雾化室温度2.7℃,内标为铊。结果: 培美曲塞和顺铂分别在10.0~600.0 ng·mL^-1(R²=0.998 0)和10.0~1 000.0 ng·mL^-1(R²=0.991 4)区间具有良好的线性范围;批内批间准确度和精密度的RSD均小于15%,培美曲塞提取回收率为(95.2±5.1)%~(123.2±3.7)%,顺铂提取回收率为(89.8±3.8)%~(101.8±13.9)%,培美曲塞与顺铂的基质效应分别为(87.5±4.3)%~(95.6±5.1)%和(85.3±1.2)%~(97.9±0.7)%,稳定性良好,符合生物样品检测要求。结论: 该套方法灵敏度高,特异性强,操作简便,检测快速,成功用于检测非小细胞肺癌患者化疗后血浆药物浓度,可为临床研究提供更多数据支撑。

Determination of plasma pemetrexed and cisplatin concentrations in patients with non-small cell lung cancer by LC-MS/MS and ICP-MS

OBJECTIVE The liquid mass spectrometry method and the inductively coupled plasma mass spectrometry method were used to determine the concentration of pemetrexed and cisplatin in human plasma, respectively, so as to provide data support for the pharmacokinetic study of the drug in the human body.METHODS For pemetrexed, ACE C18(50.0 mm×2.1 mm, 5.0 μm) was used as the column, with 0.2% formic acid in aqueous solution and 0.2% formic acid in acetonitrile as mobile phases, gradient elution was 2.9 min, and the injection volume was 20.0 μL.Electrospray ionization source, positive ion mode and multiple reaction monitoring scan mode were employed.The ion reactions used for quantitative analysis are m/z 428.2→163.1(pemetrexed), m/z 433.2→163.1(internal standard);For cisplatin, the ICP-MS peristaltic pump speed was set at 40 r·min, plasma power at 1 150 W, sample depth at 5 mm, spray chamber temperature at 2.7℃, and internal standard was thallium.RESULTS Pemetrexed and cisplatin have good linear ranges at 2.5-600.0 ng·mL^-1(R²=0.998 0) and 10.0-1 000.0 ng·mL^-1(R²=0.991 4), respectively.Their accuracy and precision were within±15%, the extraction recovery rate of pemetrexed was(95.2±5.1)%-(123.2±3.7)% while that of cisplatin was(89.8±3.8)%-(101.8±13.9)%.The matrix effect of pemetrexed was(87.5±4.3)%-(95.6±5.1)% while that of cisplatin was(85.3±1.2)%-(97.9±0.7)%.They had good stability and met the requirements for biological sample testing.CONCLUSION The method has high sensitivity, strong specificity, simple operation and rapid detection.It has been successfully used to detect the plasma drug concentration of NSCLC patients after chemotherapy, which can provide more data support for clinical research.