Toxicokinetics of strychnine and brucine after the oral administration of Biqi capsule to rats by RRLC-MS/MS.

Biqi capsule is a well-known traditional Chinese medicine formula that has been widely applied for the clinical treatment of such diseases as rheumatoid arthritis, scapulohumeral periarthritis and cervical spondylopathy. However, there is concern regarding the toxicity of Biqi capsule owing to its active ingredients, strychnine and brucine. To investigate the toxicokinetics of strychnine and brucine after oral administration of Biqi capsule to rats, a sensitive and simple rapid-resolution liquid chromatography/tandem mass spectrometry method was developed to determine the levels of strychnine and brucine in rat plasma. Chromatographic separation was performed on a Capcell Pak C18 MG II (3.0 μm, 2.0 × 35 mm) column by gradient elution with acetonitrile and 0.2% formic acid as the mobile phase. The method was validated over the range of 0.25-250 ng/mL for strychnine and 0.025-25 ng/mL for brucine. The intra- and inter-day accuracies of strychnine and brucine in rat plasma were 100.3-106.6 and 90.75-106.1% respectively, and the precisions were within 14.2%. The established method was successfully applied to the toxicokinetic study of strychnine and brucine after single and multiple oral administration of Biqi capsule to male and female rats at 0.4, 0.8 and 1.6 g/kg doses. The results showed different toxicokinetic characteristics in the different groups.