Quantification of Galantamine in Human Plasma by Validated Liquid Chromatography-Tandem Mass Spectrometry using Glimepride as an Internal Standard: Application to Bioavailability Studies in 32 Healthy Korean Subjects

• Published in: Journal of chromatographic science Vol. 50; no. 9; pp. 803 - 809
• Main Authors: Park, Yoo-Sin, Kim, Shin-Hee, Kim, Sang-Yeon, Kim, Youn-Hee, Lee, Min-Ho, Yang, Seok-Chul, Shaw, Leslie M., Kang, Ju-Seop
• Format: Journal Article
• Language: English
• Published: Niles, IL Oxford University Press 01.10.2012; Preston Publications
• Subjects: Adult; Analysis; Bioavailability; Biological and medical sciences; Biological Availability; Chromatography; Chromatography, High Pressure Liquid - methods; Chromatography, Reverse-Phase - methods; Cross-Over Studies; Galantamine - blood; Galantamine - chemistry; Galantamine - pharmacokinetics; General pharmacology; Human; Humans; Least-Squares Analysis; Linearity; Liquid chromatography; Liquid-Liquid Extraction; Liquids; Male; Mass spectrometry; Medical sciences; Pharmacology. Drug treatments; Reproducibility of Results; Republic of Korea; Sensitivity and Specificity; Sulfonylurea Compounds - analysis; Sulfonylurea Compounds - chemistry; Tandem Mass Spectrometry - methods; Therapeutic Equivalency; Asia; Korea; Republic of Korea; Biological fluid; Tandem mass spectrometry; Galantamine; Internal standard; HPLC chromatography; Esterases; Acetylcholinesterase; Solvent extraction; Electrospray; Blood; Blood plasma; Alkaloid; Sample preparation; Anticholinesterase agent; Quantitative analysis; Human; Validation; Healthy subject; Enzyme; Liquid liquid extraction; Coupled method; Oral administration; Enzyme inhibitor; Antialzheimer agent; Bioavailability; Carboxylic ester hydrolases; Parasympathomimetic; Reversed phase chromatography; Hydrolases; Pharmacokinetics
• ISSN: 0021-9665; 1945-239X; 1945-239X
• DOI: 10.1093/chromsci/bms074

A simple, rapid and selective liquid chromatography method coupled with tandem mass spectrometry is developed and validated for the quantification of galantamine in human plasma using a commercially available compound, glimepride, as an internal standard (IS). Following simple one-step liquid-liquid extraction by ethyl acetate, the analytes are separated using an isocratic mobile phase consisting of acetonitrile and 0.01M ammonium acetate (95/5, v/v) on a reverse-phase C18 column and analyzed by tandem mass spectrometry in the multiple reaction monitoring mode using the transitions of respective (M + H)+ ions, m/z 288.22 → 213.20 and m/z 491.17 → 352.30 for the quantification of galantamine and IS, respectively. The standard calibration curves show good linearity within the range of 4 to 240 ng/mL (r2 = 0.9996, 1/x2 weighting). The lower limit of quantification is 4 ng/mL. The retention times of galantamine and IS are 1.1 and 0.71 min, which showsthe high throughput potential of the proposed method. In addition, no significant metabolic compounds are found to interfere with the analysis. Acceptable precision and accuracy are obtained for the concentrations over the standard curve range. The validated method is successfully applied for pharmacokinetic and bioequivalence studies of 24 mg of a galantamine hydrobromide capsule in 32 healthy Korean subjects.