An HPLC method is described using octadecylsilica (3 microns) with an acetonitrile phosphate buffer mobile phase containing diethylamine which is capable of separating ketoconazole [(+/-)-cis-1-acetyl-4-(4[2-(dichlorophenyl)-2- (1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl)pi perazine] from four related compounds, (R049223, R063600, R053165 and R039519) and from excipients in tablets, cream and shampoo. The method was validated using an external calibration method for tablets, shampoo and creams and a standard addition method for cream. The limits of detection for the related compounds in the presence of ketoconazole are also reported.
A new HPLC method is described for the estimation of clavulanic acid. It should be of use for further studies on the penetration of clavulanic acid into body tissues and fluids. It utilizes standard HPLC equipment and UV detection, but provides at least ten-fold increased sensitivity (less than 0.008 mg/l) over previously published methods by using solid phase extraction with imidazole derivatization and subsequent pre-concentration of the sample, and a microbore chromatographic column with a conventional detection system.
Much effort and resources have been focused on improving or evolving antimalarial prophylactic regimens in order to reduce the increasing problems of malaria infection in nonimmune travelers to malaria endemic regions. Falciparum malaria in travelers returned from Africa has been attributed to reduced efficacy of chloroquine against chloroquine-resistant strains of Plasmodium falciparum (CRPF). Reported prophylaxis use by tourists from East Africa suggests only 52% admit taking their chemoprophylaxis without any missed doses. The effect of noncompliance with chloroquine (CQ) or proguanil (PG) in East Africa has been estimated as equivalent to taking no prophylaxis at all. The influence of poor compliance and/or parasite resistance on the changing pattern of malaria among travelers needs to be understood if methods of reducing morbidity are to be identified. In a number of studies, prophylaxis compliance in travelers has been collected by self-administered questionnaires from which prophylaxis efficacy of drug regimens has been calculated. The interpretation of drug efficacy has hinged on drug compliance and is controversial. We have addressed the role of chemoprophylaxis compliance in travelers with malaria using a prospective study of 368 malaria patients attending the Hospital for Tropical Diseases by examining their travel history and reported prophylaxis compliance compared to their actual plasma drug levels. This has enabled us to characterize the role of CRPF and poor compliance in the etiology of breakthrough malaria in travelers.
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