Pharmacokinetic analysis of levo-tetrahydropalmatine in rabbit plasma by rapid sample preparation and liquid chromatography–tandem mass spectrometry

• A quick and easy method was proposed for the extraction of levo-tetrahydropalmatine from plasma.
• Berberine was used as internal standard and obtained good results.
• In-housed method validation showed good performance.
• Oral bioavailability of two drug forms was compared in a pharmacokinetic study.

A rapid extraction method was developed and validated for levo-tetrahydropalmatine (l-THP) determination in rabbit plasma by liquid chromatography tandem–mass spectrometry (LC–MS/MS). The sample preparation included a single-step acetonitrile extraction and salting out liquid–liquid partitioning from the water in plasma with MgSO4. Berberine was used as internal standard. The mass spectrometry source was negative electrospray ionization. The method showed good performance in the concentration range from 5 to 200 ng mL−1. The limit of quantification (LOQ) was 1 ng mL−1. The method was successfully applied to a pharmacokinetic study in rabbit comparing the two drug formulation of l-THP including the raw material and the self-microemulsifying drug delivery system pellet.