ABSTRACT
GG167 is a novel compound which selectively inhibits viral neuraminidase and has demonstrated activity against influenza A and B. A liquid chromatography (LC) method for the determination of GG167 in human urine has been developed and validated. The method allows direct injection of urine (7 microliters) using LC column switching followed by UV detection. Initial chromatography is performed using a Nucleosil-Diol column (7 microns, 250 mm x 4.6 mm), eluted with 20 mM phosphate buffer (pH 2.5):acetonitrile (18:82, v/v) at 2.0 ml min-1. GG167 is "heart-cut" to a Spherisorb-SCX column (5 microns, 100 mm x 4.6 mm) and eluted with 35 mM phosphate buffer (pH 2.5):acetonitrile (50:50, v/v) at 1.5 ml min-1 for final separation. GG167 is detected by UV absorbance at lambda = 238 nm. UV detection and peak shape are enhanced at pH < 2.5. The quantitation range of the assay is 0.3-100 micrograms ml-1. The method has demonstrated sufficient ruggedness to be used in support of GG167 clinical trials.
Subject(s)
Antiviral Agents/urine , Enzyme Inhibitors/urine , Neuraminidase/antagonists & inhibitors , Sialic Acids/urine , Administration, Intranasal , Antiviral Agents/administration & dosage , Antiviral Agents/pharmacokinetics , Chromatography, Liquid , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/pharmacokinetics , Freezing , Guanidines , Humans , Pyrans , Quality Control , Sialic Acids/administration & dosage , Sialic Acids/pharmacokinetics , Specimen Handling , ZanamivirABSTRACT
Five pharmacokinetic methods for estimating maintenance dosage requirements of lithium carbonate were compared retrospectively in 20 inpatients with acute bipolar illness. Specific pharmacokinetic methods tested included the method of Cooper, the multiple-point method of Perry, the single-point method of Perry, the method of Zetin, and the method of Pepin. Data analysis was based on evaluation of prediction error or the difference between the predicted steady-state lithium concentration and the measured steady-state lithium concentration at equivalent daily doses. Each dosing method was assessed in regard to accuracy and bias of predicted steady-state serum lithium concentrations. Bias was assessed by comparison of the median value of the prediction error with zero. The dosing recommendation based on the Cooper nomogram resulted in a significant positive bias (p less than or equal to 0.05). Intermethod accuracy was assessed by comparison of the absolute prediction errors of each dosing method. Significant differences in accuracy were observed between the method of Pepin when compared with the single-point method of Perry (p less than or equal to 0.05, k-sample sign test). All other comparisons were nonsignificant.
