气质联用（GC／MS）研究吗啡控释片的药代动力学

Pharmacokinetic Studies of Controlled Release Tablets of Morphine by GC-MS

本实验采用磷酸可待因做内标，经液相萃取、乙酸酐衍生化处理后，用ＧＣ／ＭＳ的ＳＩＭ（选择性离子监测）定量方法测定血中吗啡的浓度。标准曲线在１．０～６０ｎｇ／ｍｌ之间呈良好的线性关系，日间日内ＲＳＤ小于９．０％，回收率可达９６％。并进行了８例肿瘤病人口服３０ｍｇ吗啡控释片、普通片的药代动力学的研究。主要的药代动力学参数：控释片和普通片的Ｃ_（ｍａｘ）分别为：１７．５、２０．８ｎｇ／ｍｌ。ｔ_（１／２）分别为５．００及１．８７ｈ，达峰时间ｔ_（ｍａｘ）分别为２．３４及１．８７ｈ。

A method for determination of morphine in plasma was developed by using the selective ion monitoring mode (SIM) in GC/MS. Codeine was used as the internal standard. Samples were hydrolyzed at pH 9. 64 and then extracted by liquid phase: toluene-n-heptane-isoamyl alcohol (7 : 2 : 1) . The plasma concentrations of morphine in cancer patients volunteers were detected by GC/MS after derivatization with acetic anhydride/pyridine. The minimum quantifiable limit is 0. 95 ng/ml. The standard curve was linear between 1. 0 to 60ng/ml, with correlation coefficients better than 0. 99, with relative standard deviation less than 9. 0%. The recovery can reach 96%. This method was applied in the studies of pharmacokinetics of morphine after given a single 30 mg oral dose of controlled release morphine tablets and regular tablets 8 cancer patients. The main pharmacokinetics parameters about controlled release tablets and regular tablets individually were as follows C_(max) were 17. 5 and 20. 8ng/ml, t_(1/2) were 5. 00 and 1. 87h.T_p were 2. 34 and 1. 87h.