Separation of vigabatrin enantiomers using mixed-mode chromatography and its application to determine the vigabatrin enantiomer levels in rat plasma

Mayu Onozato; Shusuke Uekusa; Tatsuya Sakamoto; Maho Umino; Hideaki Ichiba; Takeshi Fukushima

doi:10.1016/j.jchromb.2021.122866

Separation of vigabatrin enantiomers using mixed-mode chromatography and its application to determine the vigabatrin enantiomer levels in rat plasma

J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Aug 1:1179:122866. doi: 10.1016/j.jchromb.2021.122866. Epub 2021 Jul 27.

Authors

Mayu Onozato¹, Shusuke Uekusa², Tatsuya Sakamoto¹, Maho Umino¹, Hideaki Ichiba¹, Takeshi Fukushima³

Affiliations

¹ Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-shi, Chiba 274-8510, Japan.
² Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-shi, Chiba 274-8510, Japan; Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-shi, Chiba 274-8510, Japan.
³ Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-shi, Chiba 274-8510, Japan. Electronic address: t-fukushima@phar.toho-u.ac.jp.

PMID: 34348203
DOI: 10.1016/j.jchromb.2021.122866

Abstract

Mixed-mode chromatography-comprising a mixed phase with reversed and ionic phases, enabling hydrophobic and ion-exchange interactions simultaneously-was applied to identify vigabatrin enantiomers by HPLC with pre-column fluorescence derivatization with 2,5-dioxopyrrolidin-1-yl (4-(((2-nitrophenyl)sulfonyl)oxy)-6-(3-oxomorpholino)quinoline-2-carbonyl)prolinate (Ns-MOK-(S)-Pro-OSu). The MOK-(S)-Pro-vigabatrin enantiomers were efficiently separated within 12 min (total analysis time per sample: 28 min, including washing and equilibrium time for the column). The mobile phase was H₂O/CH₃OH/10 mM ammonium formate (pH 2.0) (20/20/60, v/v/v). Column temperature was maintained at 60℃. The proposed HPLC method could successfully monitor plasma vigabatrin enantiomer levels in rats administered (±)-vigabatrin (50 mg/kg, p.o.).

Keywords: 2,5-dioxopyrrolidin-1-yl (4-(((2-nitrophenyl)sulfonyl)oxy)-6-(3-oxomorpholino)quinoline-2-carbonyl)prolinate; Diastereomer; Fluorescence; Mixed-mode chromatography; Vigabatrin.

MeSH terms

Animals
Chromatography, High Pressure Liquid / methods*
Limit of Detection
Linear Models
Rats
Rats, Sprague-Dawley
Reproducibility of Results
Stereoisomerism
Vigabatrin* / blood
Vigabatrin* / chemistry
Vigabatrin* / isolation & purification

Substances

Vigabatrin