Development of a GC-MS method for the determination and pharmacokinetics of trans-π-oxocamphor after intravenous administration of Vitacamphorae injection in rat

Abstract

Vitacamphorae injection is an aqueous solution of trans-π-oxocamphor (TOC) mainly used to treat central respiratory problems, such as cardiac and circulatory failure. Although in clinical use for decades, bioanalytical and pharmacokinetic data for TOC are limited due to its chemical and metabolic instability. This paper reports a simple and specific method for the determination of TOC in rat blood based on gas chromatography-mass spectrometry (GC-MS). Sample preparation was limited to protein precipitation with acetonitrile after the addition of 2-nitro-1,3-dimethyl-5-tert-butylbenzene as the internal standard. Chromatography was carried out on an Agilent HP-5MS column (30 m × 0.25 mm, 0.25 μm) with temperature programming from 70 °C to 170 °C at a rate of 20 °C min⁻¹. Detection by electron impact mass spectrometry with selected ion monitoring was linear in the range of 50–5000 ng mL⁻¹ with good accuracy and precision. The method was successfully applied to a pharmacokinetic study of TOC in Sprague-Dawley rats after intravenous injection of a dose of 3.57 mg kg⁻¹. We anticipate that the assay will facilitate the further development and clinical application of Vitacamphorae injection.