Extended application of an LC-MS/MS method for the analysis of vesnarinone and its metabolites in human urine and dialysate fluid.
Vesnarinone, a positive inotropic drug developed for congestive heart failure, and its metabolites (OPC-8230, OPC-18136, OPC-18137) were analyzed in human dialysate and urine (plus an additional metabolite: OPC-18692 in urine) samples using a modification to a previously published LC-MS/MS assay for the analysis of human plasma and urine samples. OPC-8192, a structural analogue of vesnarinone, was used as the internal standard. The analytes of interest were extracted from human dialysate or urine by a solid phase extraction method using a pre-conditioned C-18 extraction column. The analytes were then resolved by a 7 min gradient elution on a reverse phase high performance liquid chromatographic column. Vesnarinone and metabolites were detected on a PE/Sciex API III+Biomolecular Mass analyzer in MS/MS mode using a Turbo IonSpray interface. The linear range of quantitation in dialysate was 2.00-100.00 ng/ml for vesnarinone and 0.50-25.00 ng/ml for each metabolite. In urine, the linear range was of 0.50-25.00 microg/ml for vesnarinone and 0.10-5.00 microg/ml for the metabolites. This method was used to support the analysis of urine and dialysate samples from renally impaired patients who are on vesnarinone treatment.
Sekar
Kumara S
KS
Department of Clinical Pharmacokinetics and Metabolism, Otsuka Maryland Research Institute, Inc., 2440 Research Blvd., Rockville, MD 20850, USA.
Bramer
Steven L
SL
D015314:Dialysis Solutions / Q000032:analysis / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D011719:Pyrazines; D011804:Quinolines / Q000378:metabolism / Q000652:urine*
D015314:Dialysis Solutions; D011719:Pyrazines; D011804:Quinolines; C041667:vesnarinone