目的 建立測定阿片堿在小鼠血漿中濃度的LC-MS/MS方法，并將該方法用于夏天無提取物在小鼠體內(nèi)的藥動學(xué)研究。方法 采用LC-MS/MS法。色譜條件采用安捷倫Zorbax C₁₈色譜柱（50 mm×2.1 mm，1.8 μm），流動相為甲醇-水（含0.1%甲酸），梯度洗脫；體積流量：0.2 mL/min；柱溫：35 ℃；進(jìn)樣量：5 μL。質(zhì)譜條件采用離子源：ESI源，正離子檢測，高純氮氣用作干燥氣（15 L/min）和氣簾氣（50 L/min），氣體溫度340 ℃；以多反應(yīng)監(jiān)測（multiple reaction monitoring，MRM）為掃描模式。采用回歸方程計算小鼠血漿中阿片堿。小鼠ig給予夏天無提取物的羧甲基纖維素鈉混懸液，制備血藥質(zhì)量濃度-時間曲線，計算藥動學(xué)參數(shù)。結(jié)果 阿片堿在0.4～200.0 ng/mL線性關(guān)系良好，精密度RSD均小于15%，準(zhǔn)確度在±15%以內(nèi)，提取回收率在90%以上，基質(zhì)效應(yīng)在90%～110%。藥動學(xué)參數(shù)最大血藥濃度（C_max）和達(dá)峰時間（t_max）分別為134.6 ng/m、1.5 h。結(jié)論 該方法適合小鼠ig夏天無提取物后阿片堿在小鼠體內(nèi)的藥動學(xué)研究。

Objetive To establish an LC-MS/MS method for the determination of protopine in plasma of mice and appliy to in vivo pharmacokinetics study of Corydalis Decumbentis Rhizoma extract in mice. Methods LC-MS/MS method was performed. The HPLC analysis was carried out on an Angilent Zorbax C₁₈ column (50 mm × 2.1 mm, 1.8 μm). The mobile phase was methanol - water (0.1% formic acid water solution) with gradient elution. The column temperature was 35 ℃ with injection volume of 5 μL at a flow rate of 0.2 mL/min. MS conditions were that a triple-quadrupole mass spectrometry equipped with electrospray ionization (ESI) source for positive ion detection and multiple reaction monitoring (MRM) were applied. Dry gas (15 L/min) and air curtain gas (50 L/min) were used as high purity N₂ with temperature 340 ℃. The contents of protopine in in plasma samples of mice were determined with regression equation of standard curves. The blood concentration-time curve was investigated after ig administration of Corydalis Decumbentis Rhizoma extract suspension prepared with sodium carboxymethyl cellulose to mice, then the pharmacokinetic parameters were calculated. Results The method was linear over the concentration ranges of 0.4 - 200 ng/mL for protopine. The RSD values of intra-day and inter-day were less than 15%, the relative error (RE) were all within 15%, and the extract recovery was above 90%. The matrix effects were between 90% and 110%. The parameters of pharmacokinetics were C_max 134.6 ng/m, and t_max 1.5 h. Conclusion The method is suitable to in vivo pharmacokinetic study of protopine in mice after ig administered Corydalis Decumbentis Rhizoma extract.

國家自然科學(xué)基金資助項目（81360485）；江西省博士后科研擇優(yōu)資助項目（贛人社字[2012]195號）；江西中醫(yī)藥大學(xué)校級課題（ZX1002）