Determination of galantamine in human plasma by LC-MS/MS using carbamazepine as an internal standard: Method validation and application to a pharmacokinetic study of galantamine hydrobromide prolonged-release capsules in healthy Thai volunteers

A rapid, sensitive and reliable LC-MS/MS method for the determination of galantamine in plasma was developed and validated for the pharmacokinetic study of galantamine hydrobromide 8 mg prolonged-release capsules. The plasma sample was prepared by simple liquid-liquid extraction with dichloromethane. Chromatographic separation was performed on a Hypurity C4 (150 x 4.6 mm, particle size 5.0 µm) using isocratic acetonitrile: 10 mM ammonium formate (90:10) as a mobile phase at a flow rate of 0.8 mL/min. Galantamine was detected by mass spectrometry using the electrospray ion source in the selected reaction monitoring mode. Carbamazepine was used as an internal standard (IS). The extraction recovery was 105.45–111.84% for galantamine and 107.35% for IS. Linearity was found within the calibration range of 0.39–62.5 ng/mL. The intra-day and inter-day accuracy were achieved with the mean concentrations of the quality control samples as 91.92–100.97% and 94.29–102.07%, respectively. The intra-day and inter-day precision were expressed as %CV of 1.34–6.11% and 3.31–5.01%. The long-term stability study showed that galantamine was stabled in plasma for at least 50 days at −30°C. This validated method was proven to be useful for the pharmacokinetic study of galantamine hydrobromide in healthy Thai volunteers. After the oral administration of one tablet in fasting conditions, Tmax and Cmax were found to be 5.61 ± 1.71 hours and 25.96 ± 4.18 ng/mL, respectively, whereas T1/2 was found to be 9.89 ± 1.48 hours