Stability-Indicating LC Method for Estimation of Nimodipine in Dosage Form and Spiked Serum Using Systematized Design of Experiments (DoE) Approach

Abstract

A simple and new liquid chromatographic method was developed and validated for the estimation of nimodipine in formulations and spiked serum samples using an analytical quality by design approach. This approach helped to define the analytical target profile and related critical analytical attributes such as retention time, theoretical plates, and tailing factor. Critical method variables such as methanol %, the flow rate of the mobile phase, and pH were identified and optimized using Box-Behnken experimental design to develop a robust method and further control strategies were developed. Chromatography for the purpose constituted of methanol: water (pH 3.5 maintained by o-phosphoric acid), 80:20, v/v as mobile phase flowing at 1.0 mL/min on a ShimPack GWS C18 column. The photodiode array detection was performed at 355 nm. Results for method validation parameters viz. linearity (0.5-80 μg/mL), accuracy (>98 %) and precision (<1 %) advocated method reliability. Chromatographic method specificity was ensured by degrading the drug forcefully. Nimodipine revealed its susceptibility to applied acid, alkali, and photolysis stress conditions, calling for adequate preventive measures. Further, the method was applied to determine suitability for the estimation of the target analyte in spiked biological fluids. Overall the method was reliable and can be applied in routine and bio-analytical purposes.

GRAPHICAL ABSTRACT

Key words:

• Designed experiments
• Nimodipine
• serum
• ultrafast liquid chromatography
• validation