Fluorescence detection of tramadol in healthy Chinese volunteers by high-performance liquid chromatography and bioequivalence assessment

Abstract

This study developed a revised high-performance liquid chromatography fluorescence method to determine plasma tramadol concentration, and thereby to examine the bioequivalence of two tramadol formulations among healthy male Chinese volunteers. The study used a double-blind, randomized, 2×2 crossover-design principle. Calculated pharmacokinetic parameters for both formulations were consistent with previous reports. According to the observation of vital signs and laboratory measurement, no subjects had any adverse reactions. The geometric mean ratios (90% confidence interval) of the test drug/reference drug for tramadol were 100.2% (95.3%-103.4%) for the area under the plasma concentration-time curve (AUC) from time zero to the last measurable concentration, 99.6% (94.2%-102.7%) for the AUC from administration to infinite time, and 100.8% (93.1%-106.4%) for maximum concentration. For the 90% confidence intervals of the test/reference AUC ratio and maximum concentration ratio of tramadol, both were in the acceptance range for bioequivalence. According to the two preparations by pharmacokinetic parameter statistics, the half-life, mean residence time, and clearance values showed no significant statistical differences. Therefore, the conclusion of this study was that the two tramadol formulations (tablets and capsules) were bioequivalent.

Keywords: bioequivalence; fluorescence detector; in vitro release; pharmacokinetic; tramadol hydrochloride.

Figures

Figure 1

Chromatograms of tramadol in plasma. Notes: (A) Blank plasma; (B) standard plasma sample; (C) plasma sample after dosing. 1, Tramadol; 2, internal standard; 3, O-desmethyltramadol.

Figure 2

In vitro release profiles of tramadol from the test and reference (50 mg). Notes: ⋄, Tablets; △, capsules. Release experiments were carried out in 0.1 M (HCL solution), at 37°C±0.5°C. Each point represents the mean value of six different experiments ± standard deviation.

Figure 3

Mean plasma concentration–time profiles of tramadol from the test and reference in healthy male Chinese volunteers (50 mg). Note: Each profile represents the mean ± standard deviation of ten volunteers.