HPLC法测定人血浆中丁咯地尔的质量浓度

目的建立测定人血浆中丁咯地尔质量浓度的HPLC法,并应用该法研究盐酸丁咯地尔片在健康人体内的药动学。方法色谱柱为Kromasil C18柱(250 mm×4.6 mm,5μm),流动相为乙腈-50mmol.L-1磷酸二氢铵缓冲液-三乙胺(体积比25∶75∶0.05),检测波长为275 nm,内标为乌拉地尔。结果丁咯地尔质量浓度线性范围为20μg.L-1～6.000 mg.L-1,回归方程为Y=0.260 5ρ-0.904×10-3,r=0.999 5,提取回收率大于87%,日内和日间RSD均小于7%。18例健康志愿者分别经口给予盐酸丁咯地尔的受试制剂和参比制剂300 mg后,血浆中丁咯地尔的tmax分别为(1.56±1.26)和(1.19±0.84)h,ρmax分别为(2.458±0.887)和(2.595±0.725)mg.L-1,t1/2分别为(4.88±1.25)和(4.96±1.42)h,AUC0-24分别为(16.275±5.931)和(16.040±5.831)mg.h.L-1,AUC0-∞分别为(17.110±6.521)和(17.008±6.782)mg.h.L-1。结论此法简便、快速,适用于盐酸丁咯地尔药动学研究以及临床上血浆药物浓度监测。

Determination of buflomedil in human plasma by HPLC

Objective To establish a high performance liquid chromatographic method for determination of the concentration of buflomedil in healthy volunteers. Methods The chromatographic separation was achieved on a Kromasil C18 column(250 mm×4.6 mm,5 μm),with acetonitrile-50 mmol·L-1 ammonium dihydrogen phosphate-triethylamine(V∶V∶V=25∶75∶0.05)as the mobile phase.The detection wavelength was set at 275 nm,and the urapidil was taken as the internal standard. Results A good linearity was obtained from 20 μg·L-1 to 6.000 mg·L-1 of buflomedil in human plasma with a regressive equation of Y=0.260 5ρ-0.904×10-3,r=0.999 5.The recoveries were above 87%,the intra-day RSD and inter-day RSD were below 7%.The pharmacokinetic analysis of buflomedil hydrochloride in 18 healthy volunteers after oral administration of 300 mg was studied.The pharmacokinetic parameters were calculated with BAPP2.0 program and the parameters were as follows:tmax=(1.56±1.26)and(1.19 ± 0.84)h,ρmax=(2.458±0.887)and(2.595±0.725)mg·L-1,t1/2=(4.88±1.25)and(4.96±1.42)h,AUC0-24=(16.275± 5.931) and(16.040±5.831)mg·h·L-1,AUC0-∞=(17.110±6.521)and(17.008±6.782)mg·h·L-1,respectively. Conclusions The method is proven to be suitable for the pharmacokinetic study of buflomedil and monitoring its concentration for the clinical application.