Determination of rimantadine in rat plasma by liquid chromatography/electrospray mass spectrometry and its application in a pharmacokinetic study.
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 microL 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.
Xu
Meijuan
M
Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China. windcolour11@hotmail.com <windcolour11@hotmail.com>
Ju
Wenzheng
W
Xia
Xiaoyan
X
Tan
Hengshan
H
Chen
Min
M
Zhang
Jun
J
Xiong
Ningning
N
Jiang
Meng
M
Chen
Lei
L
Gong
Lixiu
L
D000818:Animals; D000998:Antiviral Agents / Q000097:blood* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012299:Rimantadine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D000998:Antiviral Agents; D012299:Rimantadine