Enantioselective Box Behenken Optimized HPLC-DAD Method for the Simultaneous Estimation of Alogliptin Enantiomorphs in Pharmaceutical Formulations and their Pharmacokinetic Study in Rat Plasma.

Purpose: A stereoselective high performance liquid chromatographic analytical method with photodiode array detector was developed and validated as per the International Conference on Harmonization (ICH) guidelines for the determination of alogliptin (ALO) enantiomers in formulations and rat plasma. Methods: Enantiomeric separation was performed on a Phenomenex Lux Cellulose-2 chiral column. Box-Behnken design was used to identify the optimum conditions of the three independent variables for the desired output responses. Results: The HPLC peaks of ALO enantiomers and the internal standard pioglitazone were achieved before 8 min with a resolution of 0.77 min between R and S enantiomer and resolution of more than 2.0 between each enantiomer and pioglitazone (internal) with more than 95% recovery. The linearity range and the limit of quantification of both the enantiomers in rat plasma were 10-70 ng mL-1 and 1.2 ng mL-1 respectively. Conclusion: The developed method after validation was successfully applied for estimation of ALO enantiomers in formulations. Single oral dose of 25 mg of the ALO racemate tablets were administered to a group of 6 healthy rats for a comparative pharmacokinetic study of both the enantiomers.

Preclinical screening methods in cancer.

Cancer, a group of diseases of unregulated cell proliferation, is a leading cause of death worldwide. More than 80% of compounds which have shown promising effects in preclinical studies could not get through Phase II of clinical trials. Such high attrition rate is due to improper or selective use of preclinical modalities in anticancer drug screening. The various preclinical screening methods available such as in vitro human cancer cell lines, in vivo tumor xenograft model, or genetically engineered mouse model have their respective pros and cons. Scrupulous use of these preclinical screening methods vis-à-vis efficacy of potential anticancer compound with diverse mechanism of action can help in bringing down the rate of failure of anticancer compound at clinical phase. This article provides an insight into the various preclinical methods used in anticancer studies along with their advantages and disadvantages.