Determination of rimantadine in rat plasma by liquid chromatography/electrospray mass spectrometry and its application in a pharmacokinetic study

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2008-03, Vol.864 (1), p.123-128
• Main Authors: Xu, Meijuan, Ju, Wenzheng, Xia, Xiaoyan, Tan, Hengshan, Chen, Min, Zhang, Jun, Xiong, Ningning, Jiang, Meng, Chen, Lei, Gong, Lixiu
• Format: Article
• Language: English
• Subjects: Amantadine; Analysis; Analytical, structural and metabolic biochemistry; Animals; Antiviral Agents - blood; Antiviral Agents - pharmacokinetics; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Drug Stability; Female; Fundamental and applied biological sciences. Psychology; General pharmacology; LC/MS; Medical sciences; Pharmacokinetic study; Pharmacology. Drug treatments; Quality Control; Rats; Rats, Sprague-Dawley; Rimantadine; Rimantadine - administration & dosage; Rimantadine - blood; Rimantadine - pharmacokinetics; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization - methods
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2008.01.053

A rapid and sensitive liquid chromatography/mass spectrometry (LC/MS) method was developed and validated for the determination of rimantadine in rat plasma. Rimantadine was extracted by protein precipitation with methanol, and the chromatographic separation was performed on a C 18 column. The total analytical run time was relatively short (4.6 min), and the limit of assay quantification (LLOQ) was 2 ng/mL using 50 μL of rat plasma. Rimantadine and the internal standard (amantadine) were monitored in selected ion monitoring (SIM) mode at m/ z 180.2 and 152.1, respectively. The standard curve was linear over a concentration range from 2 to 750 ng/mL, and the correlation coefficients were greater than 0.999. The mean intra- and inter-day assay accuracy ranged from 100.1–105.0% to 100.3–104.0%, respectively, and the mean intra- and inter-day precision was between 1.3–2.3% and 1.8–3.0%, respectively. The developed assay method was successfully applied to a pharmacokinetic study in rats after oral administration of rimantadine hydrochloride at the dose of 20 mg/kg.