高效液相色谱法测定人血清和尿中盐酸青藤碱浓度及药代动力学研究

DETERMINATION OF SINOMENINE HCl IN SERUM AND URINE BY HPLC AND ITS PHARMACOKINETICS IN NORMAL VOLUNTEERS

用ＲＰＨＰＬＣ法，以三唑仑为内标，反相Ｃ１８为分析柱，乙腈—００１ｍｏｌ·Ｌ－１磷酸二氢钠—四甲基乙二胺（４６∶５４∶０２２ｖ／ｖ）为流动相，磷酸调至ｐＨ６９，检测波长２６３ｎｍ，测定血清和尿中盐酸青藤碱浓度，线性范围分别为６～４８０ｎｇ·ｍｌ－１和００６～３μｇ·ｍｌ－１，平均回收率７５８８％和９１３５％，日内日间误差小于５％，最低检测浓度血清４ｎｇ·ｍｌ－１，尿４０ｎｇ·ｍｌ－１。８名健康男性志愿者单次口服盐酸青藤碱片８０ｍｇ，测定血清及尿浓度，该药符合二室开放模型，体内消除符合一级动力学消除过程，主要药代动力学参数：Ｔ１／２α０７９１±０４９１ｈ，Ｔ１／２β９３９７±２４２５ｈ，Ｔｍａｘ１０４０±０２７４ｈ，Ｃｍａｘ２４６６０４±７１１６５ｎｇ·ｍｌ－１，ＡＵＣ２６５１１５８±１０３９０５０ｎｇ·ｈ·ｍｌ－１，ＣＬ００３３±００１ｎｇ·ｍｌ－１。

A RP HPLC method was developed to determine the concentrations of sinomenine HCl in serum and urine and its pharmacokinetics was studied in healthy volunteers. C 18 H 37 column was eluted with the mobile phase of acetonitrile—0 01 mol·L -1 sodium phosphate monobasic? ,N,N',N' tetramethylenediamine (46∶54∶0 22 v/v , pH 6 9) and the utraviolet absorbance was monitored at 263 nm. Triazolan was used as internal standard. The calibration curves were linear in the range of 6～480 ng·ml -1 in serum and 0 06～3 μg·ml -1 in urine, with mean recoveries of 75 46% and 91 38% respectively. The lowest detectable limits were 4 ng·ml -1 in serum and 40 ng·ml -1 in urine and the RSD for the intra day and inter day were less than 5%. A single oral dose of 80 mg sinomenine HCl tablet was given to 8 healthy male volunteers. The concentrations of sinomenine HCl in serum and urine were determined. The serum concentration—time curve was found to fit a two compartment open model with first order elimination. The pharmacokinetic parameters were: T 1/2 α 0 791±0 491 h, T 1/2 β 9 397±2 425 h, T max 1 040±0 274 h, C max 246 604±71 165 ng·ml -1 , AUC 2651 158±1039 050 ng·h·ml -1 , CL 0 033±0 010 ng·ml -1 .