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Dapagliflozin (DAP) is therapeutic agent for diabetes mellitus type II patients with insufficient glycemic control by exercise and diet. Stability-indicating LC–MS method was developed and validated on C8 column and method was able to separate DAP and three major hydrolytic degradation products. Structure elucidation of three major identified hydrolytic degradation products (DPs) and establishment of degradation pathway were executed with the combine application of liquid chromatography-positive mode electrospray ionization tandem mass spectrometry and high-resolution mass spectrometry. Further ProTox-II was used to predict in silico toxicity for each DPs and compared with DAP.

Timolol (TIM) is a potent β-adrenergic blocker, useful in treatment of ocular hypertension or open-angle glaucoma. Development and validation of stability indicating LCMS assay method for TIM was accomplished coherent with ICH guideline. Successful chromatographic separation of TIM with its four degradation products was attained by using gradient elution mode on reverse phase column using ammonium acetate buffer, pH 4.6 as mobile phase A and organic solvent as the mobile phase B. Chromatographic conditions were set such as 1.0 mL min−1 flow rate, 20 μL injection volume, 30 °C column temperature and 320 nm detection wavelength. Four major degradation products obtained from hydrolysis and photolysis, were identified and characterized with the combination of liquid chromatography–electrospray ionization mass spectrometry (LC–ESI/MS/MS) and accurate mass measurements. Degradation pathways were identified based on a comparison of the fragmentation pattern of the [M+H]+ ions of TIM and its degradation products. The method validation was performed as per ICH guideline Q2 (R1).

The present work describes the systematic development of a robust, precise, and rapid reversed-phase liquid chromatography method for the simultaneous determination of eprosartan mesylate and its six impurities using quality-by-design principles. The method was developed in two phases, screening and optimization. During the screening phase, the most suitable stationary phase, organic modifier, and pH were identified. The optimization was performed for secondary influential parameters--column temperature, gradient time, and flow rate using eight experiments--to examine multifactorial effects of parameters on the critical resolution and generated design space representing the robust region. A verification experiment was performed within the working design space and the model was found to be accurate. This study also describes other operating features of the column packed with superficially porous particles that allow very fast separations at pressures available in most liquid chromatography instruments. Successful chromatographic separation was achieved in less than 7 min using a fused-core C18 (100 mm × 2.1 mm, 2.6 μm) column with linear gradient elution of 10 mM ammonium formate (pH 3.0) and acetonitrile as the mobile phase. The method was validated for specificity, linearity, accuracy, precision, and robustness in compliance with the International Conference on Harmonization Q2 (R1) guidelines. The impurities were identified by liquid chromatography with mass spectrometry.

A simple, rapid, and stability-indicating RP-HPLC method for a combination of tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV) was developed and validated with the help of a suitable statistical software as an application tool for the quality by design. The drugs individually, and in combination, were subjected to forced degradation (thermal, photolytic, hydrolytic, and oxidative stress conditions) and accelerated stability studies (40 ± 1°C/75 ± 3% RH for three months). Successful separation of combined drugs from degradation products was achieved by gradient elution on a reverse-phase C18 column, using a mobile phase containing phosphate buffer (pH 3.5): acetonitrile at 1.5 mL min−1 flow rate, detection wavelength 256 nm, column oven temperature 25°C, and injection volume 10 μL. Linearity was established in the range of 20–300 μg mL−1, 24.5–367.5 μg mL−1 and 60–900 μg mL−1 for FTC, TDF, and EFV, respectively. The method was successfully applied for quantifying the drugs in marketed dosage forms and on stability samples.

Polypill is a fixed dose combination, used as a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects. In the present study, gradient LC method was developed for simultaneous determination of the Polycap, that is, Atenolol, Hydrochlorothiazide, Aspirin, Ramipril, and Simvastatin, in presence of their major interaction/degradation products. The individual drug components and their major interaction/degradation products were well separated using reverse phase C18 column and a mobile phase containing Acetonitrile:Phosphate buffer (pH 2.3). Other instrumental parameters were flow rate, 1 mL min−1; detection wavelength, 230 nm; column oven temperature, 40°C; and injection volume, 5 µL. The combined drugs were subjected to stress conditions such as hydrolysis, oxidation, photolysis, and thermal decomposition. The method was validated for linearity, precision, accuracy, specificity, and robustness.

A novel, sensitive and precise UHPLC method has been developed and validated for the simultaneous determination of the all the active components of a Polypill viz Zycad, i.e., Aspirin (ASP) Atorvastatin (ATV), Ramipril (RMP) and Metoprolol (MTP) in Zycad tablet dosage form in the presence of degradation products. Forced degradation of individual as well as combination of all the drug substances components of Polypill was conducted in accordance with ICH guidelines. Acidic, basic, neutral, and oxidative hydrolysis, thermal stress, and photolytic degradation were used to assess the stability-indicating power of the method. Use of 100 × 2.1 mm, 1.7 µm stationary phases with simple mobile phase combination buffer consisting of 0.1% Perchloric acid (adjusted to pH 2.5) and Acetonitrile, delivered in a gradient mode and quantitation was carried out using ultraviolet detection at 215 nm with a flow rate of 0.6 mL?min–1. The method was optimized using samples generated by forced degradation studies. The method was validated for linearity, accuracy (recovery), precision, Specificity and robustness. The method was linear in the range of 37.5 to 150.0 µg?mL–1 for ASP, 5.0 to 20.0 µg?mL–1 for ATV and 2.5 to 10.0 µg?mL–1 for RMP and 25.0 to 100.0 µg?mL–1 for MTP.

The present work describes the systematic development of a robust, precise, and rapid reversed-phase liquid chromatography method for the simultaneous determination of eprosartan mesylate and its six impurities using quality-by-design principles. The method was developed in two phases, screening and optimization. During the screening phase, the most suitable stationary phase, organic modifier, and pH were identified. The optimization was performed for secondary influential parameters--column temperature, gradient time, and flow rate using eight experiments--to examine multifactorial effects of parameters on the critical resolution and generated design space representing the robust region. A verification experiment was performed within the working design space and the model was found to be accurate. This study also describes other operating features of the column packed with superficially porous particles that allow very fast separations at pressures available in most liquid chromatography instruments. Successful chromatographic separation was achieved in less than 7 min using a fused-core C18 (100 mm × 2.1 mm, 2.6 μm) column with linear gradient elution of 10 mM ammonium formate (pH 3.0) and acetonitrile as the mobile phase. The method was validated for specificity, linearity, accuracy, precision, and robustness in compliance with the International Conference on Harmonization Q2 (R1) guidelines. The impurities were identified by liquid chromatography with mass spectrometry.