Determination of Bis(9)-(−)-Meptazinol, a bis-ligand for Alzheimerʹs disease, in rat plasma by liquid chromatography–tandem mass spectrometry: Application to pharmacokinetics study

A rapid, simple and sensitive LC–MS/MS method was developed and validated for the determination of Bis(9)-(−)-Meptazinol (B9M) in rat plasma. Protein precipitation method was used for sample preparation, using five volumes of methanol as the precipitation agent. The analytes were separated by a Zorbax Extend-C18 column with the mobile phase of methanol-water (containing 5 mM ammonium formate, pH 9.8) (95:5, v/v), and monitored by positive electrospray ionization in multiple reaction monitoring (MRM) mode. Retention time of IS (Bis(5)-(−)-Meptazinol) and B9M were 1.9 min and 3.3 min, respectively. The limit of detection was 0.1 ng/ml and the linear range was 1–500 ng/ml. The relative standard deviation (RSD) of intra-day and inter-day variation was 4.4–6.2% and 6.2–8.9%, respectively. The extraction recoveries of B9M in plasma were over 95%. The method proved to be applicable to the pharmacokinetic study of B9M in rat after intravenous and subcutaneous administration.