Determination of l-tetrahydropalmatine in human plasma by HPLC and pharmacokinetics of its disintegrating tablets in healthy Chinese

Abstract

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 C₁₈ column (250 mm × 4.6 mm, 5 μm), 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 μg mL⁻¹, and a linearity was obtained in the range of 0.01–1 μg 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 _1/2α of 0.74 ± 0.088 h, and eliminated slowly with t _1/2β of 11.42 ± 2.43 h. l-tetrahydropalmatine was distributed mainly in the periphery compartment with the V₁/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.