Establishment and Validation of a Stability-Indicating RP-HPLC Protocol for Mavacamten in Oral Capsule Preparations
TL;DR
A validated stability-indicating reverse-phase high-performance liquid chromatography method to quantify MYK-461 in its capsule formulation is established, offering a practical tool for routine quality control and future research, while emphasising the need for controlled storage conditions to ensure long-term drug integrity.
Abstract
Objectives Mavacamten (MYK-461), approved for hypertrophic cardiomyopathy, is a cardiac myosin inhibitor. At present, no pharmacopoeial method for its quantification has been reported. Our study was designed to establish a validated stability-indicating reverse-phase high-performance liquid chromatography method to quantify MYK-461 in its capsule formulation. Materials and Methods For chromatographic separation, an Inertsil ODS-3V C18 column (250 × 4.6 mm, 5 µm) with the mobile phase of 0.1% trifluoroacetic acid and acetonitrile (50:50 v/v) was used. The flow rate (1.0 mL/min), column temperature (35 °C), injection volume (10 µL), total run time (10 minutes), and detection wavelength (269 nm) were applied. Results The validated method showed precision, accuracy, and robustness, with relative standard deviation < 2% and recovery of 100.5%. Linearity was observed over the range 5–75 µg/mL (r = 0.9994). We achieved a clear, well-resolved separation of MYK-461 from impurities, with estimated limit of detection (1.58 µg/mL) and limit of quantification (4.8 µg/mL). In forced degradation studies, we observed the highest degradation under acidic conditions (10.37%), while minimal degradation under photolytic (0.93%), thermal (1.66 %), oxidative (2.56%), and alkaline (4.19%) conditions. Conclusion The developed method is precise and reliable, and offers a practical tool for routine quality control and future research, while emphasising the need for controlled storage conditions to ensure long-term drug integrity.