LC-MS/MS法同时测定人血浆中的6种麻黄生物碱

Determination of six ephedrine-type alkaloids in human plasma by LC-MS / MS

目的建立测定麻黄碱、伪麻黄碱、甲基麻黄碱、甲基伪麻黄碱、去甲基麻黄碱和去甲基伪麻黄碱在人血浆中浓度的LC-MS/MS方法,并将该方法用于麻黄汤口服后药物动力学研究。方法色谱柱为菲罗门Synergi Polar-RP 100 A色谱柱（50 mm×2.0 mm,2.5μm）,血浆样品经液-液萃取处理,采用梯度洗脱的方式分离,以多反应监测（multiple reaction monitoring,MRM）扫描方式检测。结果六种生物碱在线性范围内线性关系良好,日内、日间精密度（RSD）均小于15%,准确度（RE）在±15%以内,平均提取回收率在80%以上,基质效应为90%~110%。结论该方法适用于口服麻黄汤后的人体药物动力学研究。

Objective to develop an HPLC-M S / MS method to determine the concentration of ephedrine,pseudoephedrine,methylephedrine,methylpseudoephedrine,norephedrine and norpseudoephedrine in human plasma,and apply this method to the pharmacokinetics study and therapeutic drug monitoring after oral administration of mahaung decoction to the volunteers. Methods The analytes were separated on a Polar-RP column（ 50 mm × 2. 0 mm,2. 5 μm） and a triple-quadrupole mass spectrometry equipped with an electrospray ionization（ ESI） source was applied for detection. The plasma sample was prepared by a liquid-liquid extraction method. Results The calibration curves were linear over a concentration range of 0. 32-1 600. 0 μg·L- 1for ephedrine,0. 29-1 450. 0 μg·L- 1for pseudoephedrine,0. 31-1 550. 0 μg·L- 1for methylephedrine,0. 27-1 350. 0 μg·L- 1for methylpseudoephedrine,0. 26-1 300. 0 μg·L- 1for norephedrine and0. 33-1 650. 0 μg·L- 1for norpseudoephedrine. The intra-day and inter-day precision was less than 15% and the relative errors（ RE） were all within ± 15%. The recoveries for all analytes were over 80%.Conclusions The validated method was successfully applied to a clinical pharmacokinetics study and the therapeutic drug monitoring after oral administration of mahuang decoction to the male volunteers.