LC-MS/MS法测定家兔全血中的磷丙泊酚钠

Determination of fospropofol in the rabbit whole blood by LC-MS/MS

目的采用高效液物色谱一串联质谱(HPLC-MS/MS)测定家兔全血中水溶性异丙酚前药磷丙泊酚钠的浓度。方法采用Welch Ultimate XB C8柱(100 mm×2.1 mm,3μm),7-羟基香豆素为内标,流动相为5 mmol.L-1乙酸铵-乙腈(57∶43),流速0.4 mL.min-1。HPLC-MS/MS采用负离子电喷雾离子源,以多反应离子模式监测。全血样品经含内标的甲醇溶液直接沉淀蛋白后进样。结果标准曲线的线性范围是0.12～15μg.mL-1,最低定量下限为120 ng.mL-1;日内和日间RSD小于7.04%,RSD均小于8.40%。结论所用方法简便快速、准确灵敏,可用于磷丙泊酚钠血药浓度的测定和药动学的研究。

OBJECTIVE To develope a liquid chromatography-tandem mass spectrometry（HPLC-MS/MS）method for the determination of fospropofol in the rabbit whole blood.METHODS The analysis was conducted using a Welch Ultimate C18 column（100 mm×2.1 mm,3 μm）.7-hydroxycoumarin was used as internal standard.The mobile phase consisted of ammonium acetate（5 mmol·L-1） and acetonitrile（57∶43） at a flow rate of 0.4 mL·min-1.Negative electrospay ionization（ESI-） was used for LC-MS/MS determination.Quantification was performed in multiple reaction monitoring（MRM） mode.Blood samples were prepared by protein precipitation with methanol containing internal standard.RESULTS Calibration curves were established over a range of 0.12-15 μg·mL-1 with a lower quantification limit of 120 ng·mL-1.The intra-and inter-day accuracy expressed as relative error（RE） were within 7.04% and RSD were below 8.40%.CONCLUSION The method is simple,rapid,accurate,sensitive and could be used for the determination of fospropofol in blood samples and for its pharmacokinetic studies.