Liquid chromatographic assay for the non-peptidic protease inhibitor tipranavir in plasma.

Tipranavir is the most recently introduced protease inhibitor for the suppression of the human immunodeficiency virus (HIV). A selective reversed-phase liquid chromatographic assay, previously developed for atazanavir, has been extended and validated for tipranavir in plasma. Compounds were isolated from a 500 microL plasma sample using liquid-liquid extraction with dichloromethane. After evaporation and reconstitution of the extract the sample was analysed using reversed-phase liquid chromatography and ultra violet detection at 280 nm. In the evaluated concentration range (0.2-50 microg/mL tipranavir), intra-day precisions were

Liquid chromatographic assay for the protease inhibitor atazanavir in plasma.

Atazanavir is the most recently introduced protease inhibitor for the suppression of the anti-human immunodeficiency virus. A sensitive and selective reversed-phase liquid chromatographic assay for this drug in human plasma has been developed and validated. Atazanavir was isolated from a 500 microL plasma sample using liquid-liquid extraction with dichloromethane. After evaporation and reconstitution of the extract the sample was analysed using liquid chromatography and ultraviolet detection at 280 nm. In the evaluated concentration range (44-4395 ng/mL atazanavir), intra-day precisions were < or =7% and inter-day precisions were < or =14%. Accuracies between 96 and 106% were found. The lower limit of quantification was 44 ng/mL with an intra-day precision of 7%, an inter-day precision of 14% and an accuracy of 87%. There was no interference from 32 tested potentially co-administrated drugs and metabolites. The usefulness of the assay was demonstrated for samples obtained from an HIV-infected patient treated with atazanavir.

Simple high-performance liquid chromatographic assay for melphalan in perfusate, rat liver and tumour tissue.

A simple, sensitive and selective reversed-phase liquid chromatographic assay has been developed and validated for the anti-cancer agent melphalan in perfusate, liver and tumour tissue originating from isolated rat liver perfusion studies. Melphalan was extracted from the matrix using ice-cold methanol. The drug and the internal standard, propylparaben, were detected using ultraviolet absorbance at 262 nm. The assay has been validated in the 0.05-25 microg/mL range for perfusate; the lower limit of quantification (LLQ) is 0.05 microg/mL in perfusate and 0.25 ng/mg in liver and tumour tissues. Accuracies ranged from 89 to 110% and the inter-assay precisions were all below 15% (20% at the LLQ). Melphalan in a biological matrix has to be processed between 0 and 4 degrees C and is stable under all relevant processing and storage conditions tested. The assay has been exhaustively used in isolated liver perfusion studies with the drug demonstrating its applicability.