Simultaneous Determination of Dapagliflozin and Bisoprolol by LC–MS/MS: Method Development, Validation, and Forced Degradation Studies
Year: 2026
Type: preprint
Abstract: The Central Drugs Standard Control Organization (CDSCO) has approved the use of fixed dosages of bisoprolol fumarate and dapagliflozin propanediol monohydrate to treat Type 2 Diabetes Mellitus in patients with underlying hypertension and cardiovascular risk. The current work developed and validated a selective, sensitive, and stability-indicating LC–MS/MS technique for the simultaneous measurement of bisoprolol and dapagliflozin in tablet dosage forms and bulk pharmaceutical substances. Using a mobile phase of 5 mM ammonium formate with 0.1% formic acid in water (Mobile Phase A) and 5 mM ammonium formate with 0.1% formic acid in methanol (Mobile Phase B), chromatographic separation was accomplished on a Phenomenex Kinetex 2.6 µm C18 (100 Å, 150 × 4.6 mm) column. A SCIEX Triple Quadrupole 4500 mass spectrometer in positive ion mode was used for detection, using Multiple Reaction Monitoring (MRM). According to ICH recommendations, forced degradation studies were carried out using 0.1 N hydrochloric acid (acidic), 0.1 N sodium hydroxide (basic), and 3% hydrogen peroxide (oxidative), as well as thermal and photolytic stress conditions. With a correlation value R2 > 0.999, the technique efficiently separated analytes and showed acceptable stability. For bisoprolol and dapagliflozin, linearity was seen over concentration ranges of 250–2000 ng/mL and 500–4000 ng/mL, respectively. In accordance with ICH Q2(R2) requirements, the approach demonstrated appropriate accuracy, precision, and robustness, demonstrating its suitability for regular analysis.
Source: Research Square
Authors: Sushma Madhavaram, Judy Jays
Institution: M S Ramaiah University of Applied Sciences
Language: English
Subfield: Analytical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Funder: Eurostars
OpenAlex ID: W7215034443