LC-ESI-MS/MS法快速测定人血浆中帕洛诺司琼的浓度

Rapid determination of palonosetron in human plasma by LC-ESI-MS/MS

目的建立快速测定人血浆中帕洛诺司琼浓度的高效液相色谱串联质谱电喷雾检测(LC-ESI-MS/MS)法。方法以Aglent C_(18)反相柱(150 mm×4.6 mm,5μm)为色谱柱,流动相为乙腈:0.04 mol·L^(-1)甲酸铵水溶液(含0.04%甲酸)=80:20(V/V),流速0.8mL·min^(-1),柱温25℃,醋酸乙酯:二氯甲烷(4:1,V:V)为提取剂。样品经电喷雾离子源正离子化后,通过三重四级杆串联质谱仪,采用选择反应监测(SRM)模式对帕洛诺司琼(m/z 297.2→82.2)和内标地西泮(m/z285.1→154.0)进行测定。结果帕洛诺司琼高(8μg·L^(-1))、中(5μg·L^(-1))、低(0.1μg·L^(-1))3个质量浓度血浆溶液的RSD均<15%;线性范围为0.05～10μg·L^(-1),回归方程为F=1.831 9ρ+0.009 8,r=0.996 4(n=9),权重系数为1/ρ~2,分析方法的定量下限为0.05μg·L^(-1)。结论该方法灵敏、准确、简单、快速,可用于帕洛诺司琼临床血药浓度监测和药动学研究。

AIM To set up a LC-ESI-MS/MS method for palonosetron assay in human plasma. METHODS Palonosetron was extracted with ethyl acetate -dichloromethane. The residues were analyzed with a LC-ESI-MS/MS sys- tem （Agilent TC C18 column, 150 mm × 4.6 mm,5 μm） with the mobile phase consisted of acetonitrile with 0.04 mol· L^-1 arranonium formate （0.04% formic acid） = 80：20 （V/V） .The Agilent 6 410 triple quad mass spectrometer system equipped with an electrospray ionization ion-trap source was used as the detector and operated in the positive ion mode. Selected reaction monitoring（SRM） by using precursor to produce ion combinations of m/z 297.2→82.2 and m/z 285.1→154.0 was performed to detect palonosetron and the internal standard, respectively. RESULTS The average extraction recoveries for palonosetron were 78.86%, 78.35% and 80.15%, respectively. The within-day （ n = 5） and between-day （ n = 3） precision of variation was less than 15%. The calibration curve for palonosetron was linear within the range of 0.05 - 10 μg· L^- 1. The limit of quantitation for palonosetron was 0.05 μg· L^- 1 CONCLUSION The method provides a sensitive, accurate, simple and rapid analytical procedure for clinical monitoring of palonosetron and its phamacokinetic studies.