Development and validation of a stability-indicating LC-MS/MS method for simultaneous estimation of empagliflozin and metoprolol in pharmaceutical dosage forms with forced degradation studies and computational assessment of degradation products
Abstract
The empagliflozin and metoprolol FDC is currently in clinical evaluation (Phase III) for the management of type 2 diabetes mellitus associated with hypertension in India. The present study was carried out with the objective to develop and validate a sensitive, selective and stability indicating LC-MS/MS method for the simultaneous determination of empagliflozin and metoprolol in bulk drug substances and tablet formulations. Chromatography was performed using a Phenomenex Kinetex® C18 column (150 × 4.6 mm, 2.6 μm, 100 Å) with 5 mM ammonium formate in water with 0.1% formic acid (mobile phase A) and methanol with 5 mM ammonium formate and 0.1% formic acid (mobile phase B). The method showed good linearity for empagliflozin within the range of 100-4000 ng mL-1 and for metoprolol within the range of 250-10 000 ng mL-1 with correlation coefficients (R2) of 0.999 for both analytes. Validation in accordance with the ICH Q2(R2) guidelines demonstrated good accuracy, precision, specificity, robustness and sensitivity. Stability-indicating capability of the method was confirmed from forced degradation studies under acidic, alkaline, oxidative, thermal and photolytic conditions and tentative characterization of degradation products was achieved based on LC-MS/MS fragmentation patterns. To get a preliminary idea of their potential biological and toxicological significance, the suggested degradation products were further assessed using molecular docking and in silico toxicity prediction…
How strong is the evidence?
Evidence Hub reads this as a simulation / modelling, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- Strategy for Mitigating DKA Risk in Patients with Type 1 Diabetes on Adjunctive Treatment with SGLT Inhibitors: A STICH Protocol
- Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance
- SGLT2 Inhibitors in Heart Failure: Targeted Metabolomics and Energetic Metabolism
- Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors
- Sodium-glucose cotransporter inhibitors: beyond glycaemic control
- Decoding the effects of SGLT2 inhibitors on cardiac arrhythmias in heart failure
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.