ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Development and validation of an assay method for benzene in the delgocitinib drug substance using conventional HPLC

Shinkichi Nomura, Yoshiharu Ito, Shigehiko Takegami, and Tatsuya Kitade

Japan Tobacco Inc, Takatsuki, Japan

E-mail: shinkichi.nomura@jt.com

Abstract: Benzene is a highly toxic solvent that should be limited to no more than 2 ppm in drug substances, as regulated by the International Council for Harmonization guideline Q3C. We herein report an assay method for residual benzene detection in the delgocitinib drug substance using conventional high-performance liquid chromatography (HPLC). The proposed method takes advantage of the good extraction efficiency of benzene when using non-polar organic solvents, the ability of benzene to concentrate in minimum amounts of organic solvent, and the high solubility of the delgocitinib drug substance in aqueous media, resulting in salt formation as well as excellent sensitivity and selectivity. Specifically, this method uses 5 mL of 8 mol/L potassium hydroxide as an aqueous medium and 1 mL of n-hexane as organic solvent, in order to increase the resolution and sensitivity to residual benzene for HPLC. Range of the method was from 0.5 to 3 ppm according to the results of linearity, accuracy and precision, and limits of detection and quantitation of the method were 0.1 and 0.5 ppm, respectively. We expect this method to be used as a general and convenient assay of excellent sensitivity and selectivity for benzene detection, particularly when contained in water-soluble drug substances.

Keywords: Benzene ; Extraction ; Conventional HPLC ; Delgocitinib drug substance ; ICH guidelines ; Validation 

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-018-0608-2

Chemical Papers 73 (3) 673–681 (2019)