Development, validation and comparison of two stability-indicating RP-LC methods using charged aerosol and UV detectors for analysis of lisdexamfetamine dimesylate in capsules

Abstract

Two new stability-indicating liquid chromatographic methods using two detectors, an ultraviolet (UV) and a charged aerosol detector (CAD) simultaneously connected in series were validated for the assessment of lisdexamfetamine dimesylate (LDX) in capsule. The method was optimized and the influence of individual parameters on UV and CAD response and sensitivity was studied. Chromatography was performed on a Zorbax CN column (250 mm × 4.6 mm, 5 μm) in an isocratic elution mode, using acetonitrile and 20 mM ammonium formate at pH 4.0 (50:50, v/v) as mobile phase and UV detection at 207 nm. The developed method was validated according to ICH guidelines and the parameters’ specificity, limit of detection, limit of quantitation, linearity, accuracy, precision and robustness were evaluated. CAD is designated to be a non-linear detector in a wide dynamic range, however, the method was linear over the concentration range of 70–130 μg mL−1 in both detectors. The method was precise and accurate. Robustness study was performed by a Plackett–Burman design, delivering results within the acceptable range. Neither the excipients nor the degradation products showed interference in the method after studies of specificity as well as under stress conditions. The results of the LC-UV and LC-CAD methods were statistically compared through ANOVA and showed no significant difference (p > 0.05). Both proposed methods could be considered interchangeable and stability-indicating, and can be applied as an appropriate quality control tool for routine analysis of LDX in capsule.

Keywords

• Lisdexamfetamine dimesylate
• Stability-indicating
• Liquid chromatography
• Charged aerosol detector
• Stress testing
• Plackett–Burman