Li K, Zhang X, Yuan Y S, Zhao F L
Department of Instrumental Analysis, Jinling Hospital, Nanjing, People's Republic of China.
Biomed Chromatogr. 1998 Nov-Dec;12(6):326-9. doi: 10.1002/(SICI)1099-0801(199811/12)12:6<326::AID-BMC755>3.0.CO;2-M.
A simple and sensitive reversed-phase liquid chromatographic method has been developed and validated for the analysis of nicardipine in human plasma and the study of the pharmacokinetics of the drug in human body. Nicardipine and nimodipine (internal standard) in plasma were extracted with hexane-butanol (12:1, v/v) after addition of borate buffer (0.5 mol/mL, pH = 9.0), and then measured by HPLC using a Hypersil C18 column as stationary phase and acetonitrile--KH2PO4 buffer (0.015 M, pH = 5.5)--triethylamine as mobile phase. Nicardipine was quantified by ultraviolet absorbance at 236 nm. The method proved to be linear in the clinical range of 5-200 ng/mL with a regression coefficient of 0.9998. The lower limit of detection of nicardipine in plasma was 2.5 ng/mL. Intra- and inter-day coefficients of variation of assay for nicardipine in plasma were 3.5-5.4% (n = 7) and 5.2-6.4% (n = 5), respectively. The recovery of nicardipine was 92.8-100.8% for plasma. The method has been used to determine nicardipine in plasma samples from 10 volunteers and provided data on the pharmacokinetics of the drug. The results inferred that nicardipine is absorbed rapidly and has a relatively short half-life in healthy individuals. The data obtained was fitted with a 3P87 program to study the pharmacokinetics. The results showed that the disposition of nicardipine was conformed to a two-compartment open model with Tmax = 1.6 +/- 0.3 h, Cmax = 109.8 +/- 38.7 ng/mL, T1/2 = 5.35 +/- 2.28 h and AUC0-->infinity = 322.1 +/- 69.6 ng/h/mI.
已开发并验证了一种简单且灵敏的反相液相色谱法，用于分析人血浆中的尼卡地平，并研究该药物在人体内的药代动力学。在加入硼酸盐缓冲液（0.5 mol/mL，pH = 9.0）后，用己烷 - 丁醇（12:1，v/v）萃取血浆中的尼卡地平和尼莫地平（内标），然后使用Hypersil C18柱作为固定相，乙腈 - KH2PO4缓冲液（0.015 M，pH = 5.5） - 三乙胺作为流动相，通过高效液相色谱法进行测定。尼卡地平通过在236 nm处的紫外吸光度进行定量。该方法在5 - 200 ng/mL的临床范围内呈线性，回归系数为0.9998。血浆中尼卡地平的检测下限为2.5 ng/mL。血浆中尼卡地平测定的日内和日间变异系数分别为3.5 - 5.4%（n = 7）和5.2 - 6.4%（n = 5）。尼卡地平在血浆中的回收率为92.8 - 100.8%。该方法已用于测定10名志愿者血浆样本中的尼卡地平，并提供了该药物的药代动力学数据。结果推断，尼卡地平在健康个体中吸收迅速，半衰期相对较短。将获得的数据用3P87程序拟合以研究药代动力学。结果表明，尼卡地平的处置符合二室开放模型，Tmax = 1.6 +/- 0.3 h，Cmax = 109.8 +/- 38.7 ng/mL，T1/2 = 5.35 +/- 2.28 h，AUC0→∞ = 322.1 +/- 69.6 ng/h/mL。
