Analytical quality by design approach for the determination of imidazole in sildenafil API and its formulations using zwitterionic HILIC stationary phase.

Autor: Ntontis S; Laboratory of Pharmaceutical Analysis, Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, GR-54124, Greece., Tsanaktsidou E; Laboratory of Pharmaceutical Analysis, Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, GR-54124, Greece., Tzanavaras PD; Laboratory of Analytical Chemistry, School of Chemistry, Faculty of Sciences, Aristotle University of Thessaloniki, GR-54124, Greece., Kachrimanis K; Laboratory of Pharmaceutical Technology, Department of Pharmacy, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece., Markopoulou CK; Laboratory of Pharmaceutical Analysis, Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, GR-54124, Greece., Zacharis CK; Laboratory of Pharmaceutical Analysis, Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, GR-54124, Greece. Electronic address: czacharis@pharm.auth.gr.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2023 Feb 05; Vol. 224, pp. 115186. Date of Electronic Publication: 2022 Nov 26.
DOI: 10.1016/j.jpba.2022.115186
Abstrakt: Herein, the development of a HILIC method for the determination of imidazole (Imp E) in sildenafil citrate API and its final formulations is reported. The main goal of this study was to develop a robust, application-specific HPLC method according to the Analytical Quality by Design principles for the analysis of the above impurity. After the risk assessment study, the high-risk method parameters were sequentially screened and optimized by using 2-level fractional factorial and Box-Behnken designs. The mathematical models were combined with the Monte-Carlo simulations to identify the Method Operable Design Region. The method was thoroughly validated between 25 % and 150 % of the target concentration limit of the imidazole using the total-error concept. The relative bias varied between 1.6 % and 5.6 % and the RSD values were lower than 5.8 % for repeatability and intermediate precision. The limit of detection and the lower limit of quantification were satisfactory and found to be 0.025 and 0.125 μg mL -1 imidazole, respectively. The applicability of the proposed approach has been demonstrated in the analysis of several sildenafil citrate API batches and final products.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: