Analysis and pharmacokinetics of bulaquine and its major metabolite primaquine in rabbits using an LC-UV method--a pilot study.
A precise and reproducible HPLC assay has been developed and validated for simultaneous determination of bulaquine (BQ) and its metabolite primaquine (PQ) in rabbit plasma. The method, applicable to 0.5 ml plasma, involves double extraction of samples with n-hexane: isopropanol (98:2, v/v) containing dimethyl octylamine (DMOA) (0.1%, v/ v). Separations were accomplished by reversed-phase liquid chromatography using a Spheri-5 cyano column with a low pressure gradient with mobile phase consisting of ammonium acetate buffer (50 mM, pH 6.0) and acetonitrile with DMOA. The method was sensitive with a limit of quantitation of 20 ng ml(-1) in rabbit plasma for both BQ and PQ and the recoveries were > 85 and > 45%, respectively. Excellent linear relationships (r > 0.99) were obtained between the measured and added concentration ratios of the plasma concentrations over a range of 20-1000 ng ml(-1) for both the analytes. Precision and accuracy were acceptable as indicated by relative standard deviations from 1.8 to 15.1%, bias values ranging from -14.2 to 15.7%. Moreover, BQ was stable in rabbit plasma for 15 days of storage at -60 degrees C and after being subjected to three freeze-thaw cycles. The method was applied to determine the levels and pharmacokinetics of BQ in rabbits following a single 2.5 mg kg(-1) oral and intravenous dose. The BQ levels declined and the PQ levels increased with time. The PQ/BQ ratio after oral dose at 1 and 1.5 h were higher than that after intravenous dose. In the pilot preclinical pharmacokinetic study after a single 2.5 mg kg(-1) oral dose, BQ levels were determined up to 6 h (post-prandial) and 8 h (fasting). The plasma concentration versus time data were best fitted to a two-compartment open model with first-order absorption and elimination processes without lag time. The AUC(0-infinity) and the elimination t1/2 in fasted rabbit was higher than that in post-prandial rabbit indicating the effect of food on BQ pharmacokinetics.
Lal
Jawahar
J
Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Chattar Manzil Palace, P.O. Box 173, Lucknow 226001, India.
Mehrotra
Nitin
N
Gupta
Ram Chandra
RC
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000097:blood* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004355:Drug Stability; D018565:Food-Drug Interactions; D006207:Half-Life; D007202:Indicators and Reagents; D008297:Male; D011319:Primaquine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D011817:Rabbits; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet
D000962:Antimalarials; D007202:Indicators and Reagents; D011319:Primaquine; C063469:bulaquine