Determination of L-tetrahydropalmatine in human plasma by HPLC and pharmacokinetics of its disintegrating tablets in healthy Chinese
Determination of L-tetrahydropalmatine in human plasma by HPLC and pharmacokinetics of its disintegrating tablets in healthy Chinese
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DOI：
10.1007/s13318-011-0045-x
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发表时间：
2011-12-01
影响因子：
1.9
通讯作者：
Zhang Xiu-Mei
中科院分区：
文献类型：
--
作者：
Li Chao-Wu;Zhang Shuo;Zhang Xiu-Mei
建立HPLC法测定人血浆中左旋延胡索乙素的浓度，并研究健康中国人口服左旋延胡索乙素崩解片后的药代动力学。采用Phenomenex luna C-18色谱柱（250 mm × 4.6 mm，5 μ m），以甲醇-水（75：25，v/v）为移动的流动相，在281 nm波长下检测人血浆中的左旋四氢巴马汀。12名健康男性志愿者空腹过夜后单次口服左旋延胡索乙素口腔崩解片60 mg。给药前后，在计划时间采集4 mL血样。采用建立的HPLC法测定血浆中左旋四氢巴马汀的浓度，并采用Drug and Statistic（2.0版）软件对左旋四氢巴马汀的药代动力学参数进行房室模型和非房室模型的分析和评价。观察并记录崩解时间和口腔感觉。血浆中左旋四氢巴马汀的最低定量限（LLOQ）为0.01 μ g mL（-1），线性范围为0.01-1 μ g mL（-1）（r = 0.9998）。采用DAS程序，以双室开放模型系统（w = 1）拟合左旋四氢巴马汀在人体内的处置过程。延胡索乙素吸收快，t（1/2ka）为0.5 ± 0.054 h，分布快，t（1/2 α）为0.74 ± 0.088 h，消除慢，t（1/2 β）为11.42 ± 2.43 h。延胡索乙素主要分布于外周室，V-1/F为133.30 ± 30.78L。左旋延胡索乙素口腔崩解片在16 s内崩解，口感良好。该方法灵敏、快速，适用于左旋延胡索乙素的药代动力学研究和中药中左旋延胡索乙素的含量测定。左旋四氢巴马汀在人体内的代谢过程符合双房室模型（w = 1）。左旋延胡索乙素口腔崩解片口感好，耐受性好，崩解快，吸收快。
The objective of the study was to establish an HPLC method for the determination of L-tetrahydropalmatine in human plasma, and to investigate the pharmacokinetics after oral administration of L-tetrahydropalmatine disintegrating tablets in healthy Chinese. L-tetrahydropalmatine in human plasma was separated on a Phenomenex luna C-18 column (250 mm x 4.6 mm, 5 mu m), eluted using methanol-water (75: 25, v/v) as mobile phase, and detected by photodiode array detector at a wavelength of 281 nm. A single 60 mg of L-tetrahydropalmatine orally disintegrating tablets were orally given to 12 healthy male volunteers after fasting overnight. Before and after administration 4 mL of blood samples was collected at the scheduled time. The plasma concentration of L-tetrahydropalmatine was determined by the established HPLC method after disposition and its pharmacokinetic parameters were analyzed and evaluated by both compartmental and noncompartmental models using Drug and Statistic (version 2.0). The disintegrating time and the sense of mouth were observed and recorded. The lowest limit of quantification (LLOQ) for L-tetrahydropalmatine in plasma was 0.01 mu g mL(-1), and a linearity was obtained in the range of 0.01-1 mu g mL(-1) (r = 0.9998). The disposal procedure of L-tetrahydropalmatine in human was fitted using the DAS program, following a double-compartment open model system (w = 1). L-tetrahydropalmatine was absorbed quickly with t(1/2ka) of 0.5 +/- 0.054 h, distributed fast with t(1/2 alpha) of 0.74 +/- 0.088 h, and eliminated slowly with t(1/2 beta) of 11.42 +/- 2.43 h. L-tetrahydropalmatine was distributed mainly in the periphery compartment with the V-1/F of 133.30 +/- 30.78 L. L-tetrahydropalmatine orally disintegrating tablets with good taste were disintegrated in the mouth within 16 s. The established HPLC method was sensitive, rapid, and suitable for both L-tetrahydropalmatine pharmacokinetic studies and its content assay in traditional Chinese medicine (TCM). The procedure of L-tetrahydropalmatine in human was fit to double-compartmental model (w = 1). L-tetrahydropalmatine orally disintegrating tablets were palatable, well-tolerated, disintegrated and absorbed quickly.