HPLC-MS同时测定人血浆中卡马西平和苯妥英钠的血药浓度

目的 建立一种快速、灵敏并同时测定人血浆中卡马西平（CBZ）和苯妥英钠（PT）浓度的高效液相色谱-质谱联用检测方法。方法 以兰索拉唑为内标，血浆样品经乙腈沉淀后，经HPLC-MS分离分析。采用Diamonsil C18柱（2.1 mm×150 mm，5 μm），流动相：甲醇-水（含0.1%甲酸）=0.20∶0.10；流速：0.3 mL·min^-1，采用电喷雾离子源（ESI），以多反应监测方式（MRM）进行正离子监测，CBZ、PT和兰索拉唑的定量分析离子对分别为m/z 237.0/194.0，253.2/182.0，392.0/188.2。结果 CBZ在40.30-20 150.00 ng·mL^-1（r=0.993 7）内线性良好，为40.3 ng·mL^-1，低（66.08 ng·mL^-1）、中（660.8 ng·mL^-1）、高（16 120 ng·mL^-1）3个浓度的平均回收率RSD均〈15%。PT在80.1-40 050.0 ng·mL^-1（r=0.997 6）内线性良好，最低定量限为80.1 ng·mL^-1，低（133.5 ng·mL^-1）、中（1 335.00 ng·mL^-1）、高（32 040.00 ng·mL^-1）3个浓度的平均回收率RSD均〈15%。结论 该方法快速简便，灵敏准确，可用于CBZ和PT同时应用时两者的血药浓度监测及其药动学研究。

Simultaneous Determination of Carbamazepine and Phenytoin in Human Plasma by HPLC-MS

OBJECTIVE To establish a rapid and sensitive HPLC-MS method for simultaneous quantitative determination of carbamazepine（CBZ） and phenytoin（PT） in human plasma. METHODS Plasma samples were precipitated with acetonitrile and determined by HPLC-MS using lansoprazole as an internal standard. The separation was carried out on a Diamonsil C18 column（2.1 mm×150 mm, 5 μm） with a mobile phase of methanol-water（including 0.1% formic acid）（0.20∶0.10） and with a flow rate of 0.3 mL·min^-1. ESI was performed in the MRM positive mode using target ions at m/z 237.0/194.0（CBZ）, 253.2/182.0（PT）, and 392.0/188.2（lansoprazole）, respectively. RESULTS The RSD of average recovery rate for CBZ on three levels of concentration of low（66.08 ng·mL^-1）, medium （660.8 ng·mL^-1） and high （16 120 ng·mL^-1）, were 〈15%. The calibration curves of CBZ was obtained in the range of 40.3-20 150.0 ng·mL^-1（r=0.993 7） with good linearity. The low limit of quantitation was 40.3 ng·mL^-1. Meanwhile, the RSD of average recovery rate for CBZ on three levels of concentration of low （133.5 ng·mL^-1）, medium （1 335.00 ng·mL^-1） and high （32 040.00 ng·mL^-1）, were also 〈15%. The calibration curves for PT was obtained in the range of 80.1-40 050.0 ng·mL^-1（r=0.997 6） with good linearity. The low limit of quantitation was 80.1 ng·mL^-1. CONCLUSION The method provides a sensitive, accurate, precise and reliable analytical procedure for the therapeutic drug monitoring of CBZ and PT simultaneously in clinic and phamacokinetic studies.