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Adebanjo J. Adegbola ¹, Julius O. Soyinka

Affiliations
1 , ,, NG

Abstract

Malaria has been shown to strongly predispose patients in areas of malaria endemicity to bacteremia with severe outcomes, thus justifying the use of antibiotics in combination with antimalarial therapy in patients with severe malaria. This study describes a High-Performance Liquid Chromatographic (HPLC) method for simultaneous determinations of Ciprofloxacin (CPN), Quinine (QN), and its major metabolite, 3-Hydroxyquinine (3-HQN), in human plasma. Following a simple precipitation with acetonitrile, chromatographic separation was achieved on a reversed-phase Agilent Zorbax (CN) column (5 μm, 150 X 4.6 mm i.d) using a mobile phase consisting of acetonitrile: potassium dihydrogen phosphate (pH = 2.8; 0.02 M) (42:58, v/v). Retention times for CPN, 3-HQN, IS and QN were 2.7, 3.3, 3.6 and 4.9 minutes respectively. The limits of detection and validated lower limits of quantitation were 30 and 70 ng/ml for both QN and 3-HQN while the corresponding values were 50 and 100 ng/ml for CPN, respectively. The new HPLC method here developed, when compared with previous methods for the analysis of either or both drugs is simple, rapid, selective, reproducible and costeffective. It is also suitable for conducting a simultaneous therapeutic monitoring of quinine and ciprofloxacin in patients when concomittantly administered as demonstrated in five healthy volunteers.

Keywords

3-Hydroxyquinine, Ciprofloxacin, HPLC Analysis, Quinine

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Julius O. Soyinka , Adebusuyi A. Ademisoye , Cyprian O. Onyeji

Abstract

A simple, sensitive cost-effective and reproducible reverse phase high performance liquid chromatographic (HPLC) method was developed to quantitate plasma levels of proguanil (PGN) and its active metabolite, cycloguanil (CGN) in order to conduct single dose pharmacokinetic studies. The drug and the internal standard were a dded to plasma samples, vortexed and rendered alkaline with 2 M NaoH and the samples extracted with ether, evaporated to dryness and the residue was reconstituted in methanol, whi rlmixed before injecting an aliquot onto the HPLC system. The calibration plots were linear over the concentration range up to 4.0 μg /ml. The correlation coefficients (r) were of the order of 0.99 and above for both PGN and CGN. The ion pair method was carried out on a 5 μ reverse phase C-18 column, using perchlorate ion as the counter ion and ultra violet detection at 254 nm. The method was reproducible with coefficient of variation for P GN and CGN, being less than 4.0 %. PGN was well resolved from its active metabolite, CG N, and the internal standard, pyrimethamine. The limit of detection of PGN was 10 ng / ml and the recovery was greater than 95% in plasma. The analytical method therefore, exhi bits good precision and sensitivity in detecting and quantifying PGN and CGN and has bee n demonstrated to be suitable for the pharmacokinetic studies of proguanil. The clinic al applicability of the method was assessed by the preliminary pharmacokinetic study of PGN and CGN, in f ifteen healthy volunteers. The in vivo study was carried out according to a single dose randomized design.

Keywords

Proguanil, Cycloguanil, Liquid Chromatography, Pharmacokinetic Studies.

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