Development and Validation of a Solvent-Free Headspace GC-MS Method for the Screening of Benzyl Chloride in Pharmaceutical Products

Eunchae Song, Chanhong Min, Eunjae Kim, Sang Beom Han, Yong Moon Lee, Kwang Hyeon Liu, Jongki Hong, Han Bin Oh

Research output: Contribution to journalArticlepeer-review

Abstract

This study presents a solvent-free headspace gas chromatography–mass spectrometry (SF-HS-GC/MS) method for robustly screening benzyl chloride, a mutagenic carcinogen, impurities in active pharmaceutical ingredients (APIs) and drug products. The SF-HS-GC/MS method simplifies analysis by eliminating solvent use, reducing matrix interference. Optimized headspace parameters include incubation temperature, time, and sample amount. Validation, aligned with Q2(R1) ICH guidelines and ICH M7 recommendations, covers selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, system suitability, and robustness. Employing a DB-5MS column (30 m × 0.25 mm, 0.25 µm) with solvent-free split injection, the method’s calibration curve (0.05–5 μg/g) exhibits a strong correlation (>0.9998). The LOQ was 0.1 μg/g, with precision (%CV) consistently <5% and accuracy within 95–105%. Furthermore, an investigation confirmed the absence of artefactual benzyl chloride formation in drug products under headspace conditions. The developed SF-HS-GC/MS method successfully screened benzyl chloride in cinnarizine drug substances and products.

Original languageEnglish
Article number487
JournalChemosensors
Volume11
Issue number9
DOIs
Publication statusPublished - Sept 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • ICH M7
  • benzyl chloride
  • cinnarizine
  • impurity
  • solvent-free HS-GC/MS

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