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.

Development and validation of a sensitive LC-MS/MS method for pioglitazone: application towards pharmacokinetic and tissue distribution study in rats.

In the present study, a sensitive LC-MS/MS method was developed and validated to measure pioglitazone (PGZ) concentrations in rat plasma and tissues. The chromatographic separation was achieved by using a YMC Pro C18 column (100 mm × 4.6 mm, 3µ) with a mobile phase consisting of formic acid (0.1% v/v) and acetonitrile (5 : 95) at a flow rate of 0.7 mL min-1 and injection volume of 10 µL (IS: rosiglitazone). Mass spectrometric detection was done using triple quadrupole mass spectrometry using the ESI interface operating in a positive ionization mode. The developed method was validated over a linearity range of 1-500 ng mL-1 with detection and a lower quantification limit of 0.5 ng mL-1 and 1 ng mL-1. The method accuracy ranged from 95.89-98.78% (inter-day) & 93.39-97.68% (intra-day) with a precision range of 6.09-8.12% for inter-day & 7.55-9.87% for intra-day, respectively. The PGZ shows the highest C max of 495.03 ng mL-1 in plasma and the lowest C max, 24.50 ± 2.71 ng mL-1 in bone. The maximum T max of 5.00 ± 0.49 h was observed in bone and a minimum of 1.01 ± 0.05 h in plasma. The AUC(0-24 h and 0-∞) values are highest in plasma (1056.58 ± 65.78 & 1069.38 ± 77.50 ng h-1 mL-1) and lowest in brain (166.93 ± 15.70 &167.12 ± 16.77 ng h-1 mL-1), and the T 1/2 was highest in plasma (5.62 ± 0.74 h) and lowest in kidney (2.78 ± 0.19). The developed method was successfully used to measure the PGZ pharmacokinetic and tissue distribution. Further, the developed method could be utilized for validating target organ (adipose tissue) specific delivery of PGZ (nano-formulations) in addition to conventional dosage forms.

Type-II endometrial cancer: role of adipokines.

BACKGROUND: Type-II endometrial cancer is an estrogen independent and one of the most lethal types of cancer having poor prognosis. Adipokines play a crucial role in the triggering Type-II EMC. In addition, adipokines modulators, therefore, may have beneficial effects in the treatment of Type-II endometrial cancer, which was clinically evidenced. AREAS COVERED: This review presents the role of various adipokines involved and also the suitable modulators to treat Type-II endometrial cancer. CONCLUSION: In the present review, we try to discuss the role of individual adipokines in the pathogenesis of Type-II endometrial cancer, and also the possible beneficial effects of adipokines modulator in the treatment of Type-II endometrial cancer.

Possible role of Thiazolidinedione in the management of Type-II Endometrial Cancer.

Type-II Endometrial Cancer (EMC) is one of the most common types of gynaecological cancer affecting more than 2.7 million people worldwide. Clinical evidence shows that adipokines levels are abnormally altered in Type-II EMC and reported to be one of the major responsible factor for uncontrolled proliferation and metastasis in Type-II EMC. Reversing the altered adipokine levels, therefore, help to control Type-II EMC proliferation and metastasis. In the present hypothesis we focus on the possible role of Thiazolidinediones in favourably altering the adipokine levels to benefit in the management of Type-II EMC.