Determination of secnidazole in human plasma by high-performance liquid chromatography with UV detection and its application to the bioequivalence studies.
A simple, accurate, precise and sensitive HPLC-UV method was developed for the determination of secnidazole in human plasma. Secnidazole and tinidazole (IS) were extracted from 0.2 mL of human plasma by ethyl acetate. Secnidazole was then separated by HPLC on a Diamond C(18) column and quantified by ultraviolet detection at 319 nm. The mobile phase consisted of acetonitrile-aqueous 5 mm sodium acetate (30:70, v/v) containing of 0.1% acetic acid adjusted to pH 4.0, and the flow rate was 1.0 mL/min. The low limit of quantification was 0.1 microg/mL. The method was linear over the concentration range 0.1-25.0 microg/mL (R(2) = 1.000). The recovery of secnidazole from human plasma ranged from 76.5 to 89.1%. Inter- and intra-assay precision ranged from 3.3 to 10.7%. Secnidazole in plasma was stable when stored at ambient temperature for 8 h, at -20 degrees C for 2 weeks and at -20 degrees C for three freeze-thaw cycles. The developed method was successfully applied to the pharmacokinetic and bioequivalence studies between test and reference secnidazole tablets following a single 500 mg oral dosage to 20 healthy volunteers of both genders. Pharmacokinetics parameters T(max), C(max), AUC(0-)t, AUC(0-infinity), T(1/2) were determined of both preparations. The analysis of variance (ANOVA) did not show any significant difference between the two preparations and 90% confidence intervals fell within the acceptable range for bioequivalence. It was concluded that the two secnidazole preparations are bioequivalence and may be used interchangeably.
Li
Xiaoyu
X
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Box 210, 24# Tongjia Xiang Street, Nanjing 210009, People's Republic of China.
Sun
Jianguo
J
Wang
Guangji
G
Zheng
Yuanting
Y
Yan
Bei
B
Xie
Haitang
H
Gu
Yi
Y
Ren
Hongchan
H
D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000494:pharmacology; D019540:Area Under Curve; D001682:Biological Availability; D002138:Calibration / Q000592:standards; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D010949:Plasma / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*; D013810:Therapeutic Equivalency; D014011:Tinidazole / Q000592:standards
D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D014011:Tinidazole; D008795:Metronidazole; C016724:secnidazole