An improved LC–ESI–MS–MS method for simultaneous quantitation of rosiglitazone and N-desmethyl rosiglitazone in human plasma

A fast, sensitive, and selective method for the simultaneous quantitation of rosiglitazone and N-desmethyl rosiglitazone in human plasma, using rosiglitazone-d4 and N-desmethyl rosiglitazone-d4 as the respective internal standards, has been developed and validated. The analytes in human plasma (50 μL sample aliquot) were isolated through supported liquid/liquid extraction (SLE) and separated by isocratic HPLC over a 3-min period. The precursor and product ions were detected by ESI–MS–MS with multiple reaction monitoring (MRM) in a triple quadrupole mass spectrometer. For both rosiglitazone and N-desmethyl rosiglitazone, the lower limit of quantitation (LLOQ) was 1.00 ng/mL, and the quantitation range was 1.00–500 ng/mL (with an average correlation coefficient >0.9990). The intra-assay and inter-assay precision had a maximum %CV of 9.37%, and the accuracy had a maximum %difference from theoretical of 12.7%. This method was applied to a clinical study where 16 healthy volunteers were administered a single dose of 4.0 mg rosiglitazone. The pharmacokinetic parameters of rosiglitazone and N-desmethyl rosiglitazone were consistent with the results reported in the literature.