Quantification of rosiglitazone in rat plasma and tissues via LC-MS/MS: Method development, validation, and application in pharmacokinetic and tissue distribution studies.

A bioanalytical method for the quantification of rosiglitazone in rat plasma and tissues (adipose tissue, heart, brain, bone, and kidney) using LC-MS/MS was developed and validated. Chromatographic separation was achieved on a Gemini C18 column (50 × 4.6 mm, 3 µm) using a mobile phase consisting of 10 mM ammonium formate (pH 4.0) and acetonitrile (10:90, v/v) at a flow rate of 0.8 mL/min and injection volume of 10 µL (internal standard: pioglitazone). LC-MS detection was performed with multiple reaction monitoring mode using target ions at m/z → 358.0 and m/z → 357.67 for rosiglitazone and pioglitazone (internal standard), respectively. The calibration curve showed a good correlation coefficient (r2 ) over the concentration range of 1-10,000 ng/mL. The mean percentage recoveries of rosiglitazone were found to be over the range of 92.54-96.64%, with detection and lower quantification limit of 0.6 and 1.0 ng/mL, respectively. The developed method was validated per U.S. Food and Drug Administration guidelines and successfully utilized to measure rosiglitazone in plasma and tissue samples. Further, the developed method can be utilized for validating specific organ-targeting delivery systems of rosiglitazone in addition to conventional dosage forms.

A stability-indicating LC-MS/MS method optimization for Pemetrexed through design of experiments: Identification and characterization of major oxidative degradation product.

A stability-indicating high-performance liquid chromatography method for Pemetrexed bulk was developed and validated as per the ICH guidelines by employing design of experiments methodology equipped with Box-Behnken design. The separation of Pemetrexed and its oxidative degradation product was achieved in isocratic elution mode with Zorbax C18 column (150 mm x 4.6 mm x5 µm) using 10 mM ammonium acetate (pH 4.5 adjusted with acetic acid) and acetonitrile in the ratio of 50:50, v/v with a flow rate of 1.0 mL/min at detection wavelength of 223 nm. Tandem mass spectrometry method was adopted to identify and characterize the major oxidative degradation product. The results obtained indicate that the method is specific, linear, precise and accurate for the determination of Pemetrexed and characterization of degradation product.

A simple sensitive UFLC-MS/MS method for the simultaneous quantification of artesunate, dihydroartemisinin and quercetin in rat plasma and its application to pharmacokinetic studies.

An ultrafast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method was developed for the simultaneous estimation of artesunate (ART), dihydroartemisinin (DHA, an active metabolite of ART) and quercetin (QRT) in rat plasma. The separation was achieved using a Zorbax C18 column (3 µm, 50 mm × 4.6 mm) as a stationary phase with a mobile phase of 0.1% formic acid (10% by volume) and methanol (90% by volume) at a flow rate of 0.4 mL min-1 and an injection volume of 10 µL. Artemisinin (ATM) was used as the internal standard (IS). Mass detection was performed by electrospray ionization (ESI)-tandem mass spectrometry via multiple reaction monitoring (MRM) in positive mode except for QRT, where negative ionization was used. The extraction recoveries of ART, DHA, and QRT from plasma were found to be 91.05-99.62%, 95.12-98.56% and 89.35-98.90%, respectively. The developed method was validated and successfully applied to the quantitative analysis of ART, DHA and QRT in plasma samples after the oral administration of ART and ART-QRT pure drugs to rats at the dose of 5 mg kg-1 each. The results reveal that the developed method can be further used for the quantification of the proposed combination drugs in nanoformulations.