Development and validation of a liquid chromatography mass spectrometry method for the determination of donepezil in human plasma

Abstract

Aim

A selective, and sensitive LC–MS/MS method has been developed and validated for quantification of donepezil in human plasma using donepezil D7 as an internal standard (IS).

Methods

The analyte and IS were extracted by liquid–liquid extraction using dichloromethane and hexane mixture and separated by isocratic elution on C18 analytical column with 0.1% formic acid and methanol in the ratio of 70:30 (flow rate of 1 ml/min) as the mobile phase in the positive ion mode. Multiple Reaction Monitoring transitions for donepezil and internal standard are 380.2/91.2 and 387.2/98.2 respectively.

Results

The lower limit of quantification was 50 pg/ml with the linearity range of 50 pg/ml–25,000 pg/ml and the method was validated as per international regulatory guidelines for its selectivity, stability, accuracy, precision, and recovery.

Conclusion

The method can be readily applicable to pharmacokinetic and bioequivalence studies to support different regulatory submissions.