Sensitive and selective liquid chromatography-mass spectrometry method for the quantification of rosiglitazone in human plasma.

A sensitive and selective high-performance liquid chromatography-electrospray ionisation-tandem mass spectrometry (HPLC-ESI-MS-MS) method for determination of rosiglitazone in human plasma has been developed. After the addition of the internal standard, plasma samples were precipitated by acetonitrile. The compounds were separated on a proC18 column using a mixture of ammonium acetate buffer (0.02 M, pH 6.5) and acetonitrile (in the ratio of 47:53, v/v) as mobile phase. A Finnigan LCQdeca plus ion trap mass spectrometer connected to a Finnigan Surveyor HPLC was used to develop and validate the method. Linearity was established for the range of concentrations 1-1000 ng/ml with a coefficient of determination (r(2)) of 0.999. The intra-day accuracy for rosiglitazone ranged from 110.0 to 99.2% at low, medium and high levels. The inter-day accuracy was less than 15%. The lower limit of quantitation (LLOQ) was identified reproducible at 1.0 ng/ml with a precision of 5.7%. After validation, the method was used to study the pharmacokinetic profile of rosiglitazone in five healthy volunteers after administration of a single oral dose (4.0mg). The proposed method enabled the unambiguous evaluation and quantitation of rosiglitazone for pharmacokinetic, bioavailability or drug-drug interaction studies. A possible chromatography peak (m/z 121, its parent ion m/z 344) of N-demethyl rosiglitazone was observed at 3.49 min during determining rosiglitazone. This may be also a potential method for simultaneous determination of rosiglitazone and its metabolite N-demethyl rosiglitazone concentrations in plasma.