HPLC-UV method for assaying 99/357, a synthetic trioxane antimalarial derivative in rat and rabbit serum.
In the present study an accurate and precise HPLC-UV assay method in rat and rabbit serum has been developed and validated for determination of 99/357--a new synthetic analogue of artemisinin developed by Central Drug Research Institute (CDRI), of the class of trioxane derivative. Separation was achieved using a C-18 reversed phase column with a mobile phase comprising of acetonitrile and deionized water (80:20%, v/v) using a UV detector, set at a wavelength of 266 nm. The method, applicable to 200 microl serum, involved double extraction of the samples with 20% isopropyl alcohol (IPA) in n-hexane. The recovery of 99/357 in the two matrices was >90%. The method was sensitive with a limit of quantitation of 25 ng/ml in both rat and rabbit matrices. Precision and accuracy were within the acceptable limits, as indicated by relative standard deviation (accuracy) varying from -12.7 to 5.7% and bias (precision) values ranging from 0.6 to 11.8%. Moreover, 99/357 was stable in serum up to 30 days of storage at -60 degrees C and after being subjected to three freeze/thaw cycles. The method will be applied to perform pharmacokinetic studies of 99/357.
Singh
S K
SK
Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow-226001, India.
Singh
Rajendra Pratap
RP
Gupta
R C
RC
D000818:Animals; D000962:Antimalarials / Q000097:blood*; D037621:Artemisinins / Q000097:blood*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D011817:Rabbits; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results; D012717:Sesquiterpenes / Q000097:blood*; D013056:Spectrophotometry, Ultraviolet
C499892:99-357 compound; D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes