Determination of the stoichiometry between a drug and its counter-ion by supercritical fluid chromatography using ultra-violet and evaporative light scattering detections: Application to ondansetron hydrochloride

Pauline Bouchot; Catherine Foulon; Marie Lecoeur

doi:10.1016/j.talanta.2020.121166

Determination of the stoichiometry between a drug and its counter-ion by supercritical fluid chromatography using ultra-violet and evaporative light scattering detections: Application to ondansetron hydrochloride

Talanta. 2020 Oct 1:218:121166. doi: 10.1016/j.talanta.2020.121166. Epub 2020 May 22.

Authors

Pauline Bouchot¹, Catherine Foulon¹, Marie Lecoeur²

Affiliations

¹ Univ Lille, CHU Lille, ULR 7365, GRITA, Groupe de Recherche sur Les Formes Injectables et Technologies Associées, F-59000, Lille, France.
² Univ Lille, CHU Lille, ULR 7365, GRITA, Groupe de Recherche sur Les Formes Injectables et Technologies Associées, F-59000, Lille, France. Electronic address: marie.lecoeur@univ-lille.fr.

PMID: 32797919
DOI: 10.1016/j.talanta.2020.121166

Abstract

In this paper, a supercritical fluid chromatography method using ultra-violet and evaporative light scattering detections (SFC-UV/ELSD) has been developed and validated for the stoichiometry determination of an antiemetic drug with its counter-ion i.e. ondansetron hydrochloride. Seven stationary phases were first screened using a CO₂-methanol-diethylamine mobile phase. Best conditions were determined using Derringer's desirability functions regarding chromatographic separation: selectivity, resolution, peak shape and runtime. The influence of co-solvent composition on resolution was evaluated. After optimization, best chromatographic results were obtained using 2-ethylpyridine stationary phase and a co-solvent composed of 0.2% diethylamine and 2% water in methanol. While ondansetron was quantified using UV detection (214 nm) and an external calibration curve, the determination of chloride was carried out using ELSD and an internal calibration curve. Then, the method was validated using the accuracy profile approach with a total error included in the ±10%. Finally, the proposed method was applied for the determination of the molar ratio between ondansetron and chloride. A value of 1.001 ± 0.003 demonstrated that the stoichiometry of this drug with its counter-ion was 1:1.

Keywords: 2-Ethylpyridine stationary phase (2-EP); Evaporative light scattering detector (ELSD); Ondansetron hydrochloride; Stoichiometry; Supercritical fluid chromatography (SFC).