Determination of pharmacokinetics of itraconazole in healthy Indian subjects under fed condition and incurred sample analysis using a validated liquid chromatography tandem mass spectrometric method

Abstract

This study aimed to determine Itraconazole Pharmacokinetics in healthy Indian subjects under fed condition and incurred sample analysis in human plasma by using a validated liquid chromatography tandem mass spectrometric method. A study in healthy human Indian subjects under fed condition was conducted to determine pharmacokinetics of two treatments of Itraconazole 100 mg capsules. Method validation was performed as per USFDA guidelines. Incurred Sample Reanalysis (ISR) was performed by random selection of subject samples. All the method validation parameters were found to be acceptable in terms of accuracy and precision. Results of all stability exercises in human plasma were within acceptable limits. The validated LCMS/MS method was used for sample analysis. A value of 96.7% for Itraconazole and 92.2% for Hydroxy Itraconazole was observed for incurred sample re-analysis. Arithmetic means for Cmax and AUC0→∞ were 103.699, 95.105 ng/ml and 1665.599, 1556.486 ng/ml.h, respectively, for Itraconazole and for Hydroxy itraconazole Cmax and AUC0→∞ were 179.436, 173.037 ng/ml and 4136.456, 4049.746 ng/ml.h, respectively, in treatment 1 and 2. In conclusion, a LCMS/MS method for quantification of Itraconazole and Hydroxy Itraconazole was used for analysis of clinical samples and determination of pharmacokinetic of Itraconazole in a fed study in an Indian population. Incurred sample re-analysis data indicate good acceptance and reproducibility of the method.