A simple and rapid high-performance liquid chromatography method for determination of alendronate sodium in beagle dog plasma with application to preclinical pharmacokinetic study.
A simple and rapid high performance liquid chromatographic (HPLC) method for quantifying alendronate in beagle dog plasma was developed, validated and applied to a pharmacokinetic study. The sample preparation involved coprecipitation with CaCl(2) and derivatization with o-phthalaldehyde. Chromatographic separation was achieved on a Diamonsil C(18 )(250 x 4.6 mm, 5 microm) using acetonitrile-0.4% EDTA-Na(2) (16:84, v/v) containing 0.034% of NaOH as mobile phase. The fluorimetric detector was operated at 339 nm (excitation) and 447 nm (emission). The linearity over the concentration range of 5.00-600 ng/mL for alendronate was obtained and the lower limit of quantification was 5.00 ng/mL. For each level of quality control samples, inter-day and intra-day precisions were less than 8.52 and 7.42% and accuracies were less than 9.07%. The assay was applied to the analysis of samples from a pharmacokinetic study. Following the oral administration of 70 mg alendronate sodium to beagle dogs, the maximum plasma concentration (C(max)) and elimination half-life were 152 +/- 27.3 and 1.75 +/- 0.267 h, respectively. The method was demonstrated to be highly feasible and reproducible for pharmacokinetic studies.
Meng
Jian
J
Shanghai Institute of Materia Media, Chinese Academy of Science, 646 Songtao Road, Shanghai 201203, China. goodwill_123@163.com
Meng
Qiang
Q
Zheng
Liangyuan
L
D019386:Alendronate / Q000097:blood* / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D050071:Bone Density Conservation Agents / Q000097:blood* / Q000493:pharmacokinetics*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D010949:Plasma / Q000737:chemistry; D012015:Reference Standards; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence
D050071:Bone Density Conservation Agents; D007202:Indicators and Reagents; D019386:Alendronate