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Imatinib has been successful in the management of chronic myeloid leukemia (CML) but some patients experience adverse reactions or develop resistance to its use. The roles of some polymorphisms in genes encoding enzymes critical for the biotransformation of imatinib have been previously examined. This study, hence, evaluated some other unstudied functionally significant polymorphisms in CYP1A2, CYP2C8, CYP2C9, and CYP3A5. Trough imatinib blood levels and genotypes were determined in 42 CML patients by an HPLC-UV technique and a Sequenom iPLEX assay, respectively. Statistical analysis of the influence of genetic polymorphisms on standardized trough level detected no significant relationship. However, higher trough levels were observed in two homozygous carriers of CYP2C8*2 while diminished imatinib levels were seen in two homozygous carriers of CYP3A5*7. The study findings suggest that polymorphisms in drug metabolizing enzymes may be significant for imatinib therapy only in instances where all copies of the relevant studied genes are functionally impaired. [ABSTRACT FROM AUTHOR]

Purpose: To develop a simple, sensitive and selective method for the determination of dextromethorphan and its metabolite, dextrophan in human urine using reversed-phase high performance liquid chromatography with UV-spectrophotometric detection (RP-HPLC-UV). Methods: Pre-column sample clean-up was carried out by liquid-liquid extraction of the analytes with chloroform: isopropanol (70:30) solution after alkalization of 1000 µL sample and spiking of internal standard, morphine. The samples were chromatographed in a reversed-phase (C-18) ultra sphere silica (5µm particle size and 250 x 4.6 mm I.D). The mobile phase consisted of methanol: acetonitrile: 0.5% w/v ammonium acetate (10:10:80) adjusted to pH 2.8 with orthophosphoric acid and pumped through the column at 1ml/min flow rate. The analytical method was validated for accuracy and precision as well as the recovery of the analytes, dextromethorphan and its metabolite, dextrophan over the concentration range of 0.20 to 5.0µg/ml. Results: The standard curves were linear over the concentration range of 0.2 to 5.0µg/ml for dextromethorphan and dextrorphan. The regression coefficients (R²) of the analytes were >0.99. The method was reproducible with coefficient of variation for the analytes being < 10 %. Dextromethorphan was well resolved from its metabolite, dextrorphan and the internal standard, morphine. The limits of detection of dextromethorphan and dextrorphan were 50ng/ml and the recoveries and accuracies were greater than 85 and 90 %, respectively. Conclusion: The analytical assay method exhibits good precision and selectivity and it was applied to the analysis of dextromethorphan and dextrorphan in urine for the assessment of CYP2D6 activity. [ABSTRACT FROM AUTHOR]

Background and Aim: Vitamin A deficiency (VAD) constitutes a major nutritional concern in developing countries. It contributes significantly to the morbidity and mortality of under-five children and can result in impaired resistance to infection as well as increased risk of death. The aim of this study was to determine the prevalence of VAD among Southwestern Nigerian children., Methods: Apparently healthy children aged between 6 months and 5 years were recruited for the study. Their serum retinol levels were determined by high-performance liquid chromatography., Results: Of the 170 children studied, nine (5.3%) had VAD, although none had severe VAD. The prevalence of VAD did not show statistically significant variation with age (P = 0.159), sex (P = 1.000), social class (P = 0.740), immunisation status (P = 0.197) or nutritional status (P = 0.090)., Conclusion: The prevalence of VAD among Nigerian children appears to have reduced, compared with previous reports; however, further studies are required to assess the current national prevalence, so as to design programmes that can achieve further reduction in the proportion of children affected., Competing Interests: There are no conflicts of interest