HPLC method development for fampridine using Analytical Quality by Design approach

• Published in: Acta Pharmaceutica 2020-12, Vol.70 (4), p.465-482
• Main Authors: Kovács, Béla, Boda, Francisc, Fülöp, Ibolya, Székely-Szentmiklósi, István, Kelemen, Éva Katalin, Kovács-Deák, Boglárka, Székely-Szentmiklósi, Blanka
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine - analysis; Analytical Quality by Design; Chromatography, High Pressure Liquid - methods; Delayed-Action Preparations - analysis; Design of experiments; Dosage Forms; Drug Design; Elution; Excipients; Experimental design; fampridine; High-performance liquid chromatography; HPLC; Indicators and Reagents; Limit of Detection; Linearity; Liquid chromatography; Multivariate analysis; Potassium Channel Blockers - analysis; Quality Control; Reproducibility of Results; Signal detection; Signal Processing, Computer-Assisted; Tablets
• ISSN: 1846-9558; 1330-0075; 1846-9558
• DOI: 10.2478/acph-2020-0036

Offering a systematic and multivariate analysis of the analytical procedure, development and validation of HPLC methods using Quality by Design approach are in the limelight of current research trends. A new, experimental design-aided HPLC method for fampridine was developed and preliminarily validated according to current in-force international guidelines for linearity, accuracy, robustness and precision. The method offers a high throughput sample analysis, with an elution time of 2.9 minutes, and signal detection without excipient interference performed at 262 nm. The method proved to be linear between 1–15 µg mL ( = 0.9996). The mean recovery was found to be 98.7 ± 1.9 % in the tested range of 2.5–7.5 µg mL . Low RSD values (< 1 %) were obtained for both model, intra- and inter-day precision. The limit of detection and limit of quantification were 0.24 and 0.78 µg mL , resp. The method proved to be applicable for active substance assay in a pharmaceutical dosage form.