The population pharmacokinetic approach developed in this study should allow dosage to be individualized in order to decrease toxicity while maintaining good efficacy.
A high-performance liquid chromatographic (HPLC) method for the determination of melphalan in human plasma was developed. This method involved a solid phase extraction (SPE) of melphalan and the internal standard (propylparaben) from plasma, using bond Elut C2 SPE ORDER REPRINTS columns with an elution solvent of 0.5 mL of acetonitrile-purified water (50 : 50, v/v). Separation of the two analytes was achieved within 15 min, using a reversed-phase Kromasil C18 analytical column (150 Â 4.6 mm I.D., 5 mm particle size) with a mobile phase of methanol -water -acetic acid (48 : 51 : 1, v/v). An ultraviolet detector operated at 261 nm was used, with a linear response observed from 10 to 250 ng mL 21 . Obtained from the method validation, inter-assay precision was below 6% and accuracy is near 100%. The extraction efficiency of the assay was approximately 71% and was constant across the calibration range. The lower limit of quantitation was 10 ng mL 21 ; at this level, precision was 5% and accuracy was 101%. The applicability of this method has been demonstrated by the successful analysis of clinical plasma samples. The SPE procedure developed in this paper, to quantify melphalan in biological samples requiring three steps for sample loading, clean-up, and elution, can easily be automated by using either a robot or an automated sample preparation system.
Collecting data systematically about adverse effects which might be caused by drugs is essential for orphan diseases in order to detect potential adverse effects which cannot be suspected at first.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.