LC-MS/MS CHARACTERIZATION OF FORCED DEGRADATION PRODUCTS OF TUCATINIB, A NOVEL TYROSINE KINASE INHIBITOR: DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD

Objective: The current study focused on the development, validation, and characterization of forced degradation products using LC-MS/MS. Methods: A simple, selective, validated and well-defined isocratic HPLC methodology for the quantitative determination of Tucatinib at a wavelength of 239 nm. An isocratic elution of samples was performed on an Inertsil ODS (250x4.6 mm, 5m) column with a mobile phase of 70:30v/v Acetonitrile and formic acid (0.1%) delivered at a flow rate of 1.0 ml/min. MS/MS was used to characterize degradation products formed in the forced degradation study. The validation and characterization of forced degradation products were performed in accordance with ICH guidelines. Results: Over the concentration range of 5-100μg/ml, a good linear response was obtained. Tucatinib's LOD and LOQ were determined to be 0.05 and 0.5, respectively. According to standard guidelines, the method was quantitatively evaluated in terms of system suitability, linearity, precision, accuracy, and robustness, and the results were found to be within acceptable limits. The drug was degraded under acidic, alkaline, and reduction conditions in forced degradation studies. Conclusion: The method was found to be applicable for routine tucatinib analysis. Because no LC-MS/MS method for estimating tucatinib and its degradation products has been reported in the literature. There is a need to develop a method for studying the entire tucatinib degradation pathway.

DEVELOPMENT OF FORCED DEGRADATION STUDIES OF FAVIPIRAVIR BY RP-HPLC

Forced degradation studies and stability indicating method were developed for the estimation of Favipiravir by reverse phase High performance liquid chromatography in active Pharmaceutical ingredient and its tablet dosage form. The method was achieved by using C18 column (250 X 4.6mm X 4µm) with mobile phase mixture ortho phosphoric acid and acetonitrile in the ratio 60:40. The mobile phase was allowed to pump with the flow rate 1ml/min by maintaining detection wavelength at 324nm using ultra-violet detector. Favipiravir drug was subjected to various stress conditions according to International Conference of Harmonization Q1A(R2) guidelines to establish stability indicating method. Favipiravir drug was found to be sensitive at peroxide degradation. The impurity peak was characterized by mass spectral studies. The method was validated for analytical standards such as linearity, accuracy, Precision, sensitivity and robustness. A rapid and sensitive method was developed for the estimation of favipiravir which indicates its stability indicating behavior.

Development and Stability of Forced Degradation Studies Indicating Different Brands of Metformin Drugs

In present study, Accouring to specification of Indian pharmacopeia the content official limit of not less than (98.5%) and not more than (101.0%) of the lable amount our hypothesis was that when all different brands of metformin were expose to the different degradation parameters. The Forced degradation studies show the chemical behavior of the molecule which in turn helps in the development of formulation and package. A forced degradation study is an essential step in the design of a regulatory compliant stability program for both drug substances and products, and formalized as a regulatory requirement in ICH Guideline Q1A in 1993. Forced degradation is a degradation of new drug substance and drug product at conditions more severe than accelerated conditions.

A new Validated Stability Indicating RP-UFLC Method for the Estimation of Voriconazole in presence of internal standard

Voriconazole is used for the treatment of variety of fungal infections caused by aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis etc. Voriconazole belongs to triazole class. Voriconazole is mainly used to treat certain patients who are not responding to other anti-fungal drugs. It works by slowing the growth of the fungi that cause infection. A new validated reverse phase stability indicating liquid chromatographic method has been developed for the assay of Voriconazole in presence of an internal standard (Rufinamide) tablets. Forced degradation studies were performed to define the selectivity and specificity of the method. Linearity was observed over the concentration range 1.0-100μg/mL with linear regression equation y = 0.4489x – 0.1262 (r2 = 0.9999). The LOQ and LOD were found to be 0.8934μg/mL and 0.2921μg/mL. The present stability indicating RP-UFLC method was validated as per ICH guidelines and can be useful for the assay of tablets and injections and also for the kinetic studies.