title: Quantification of residual solvents in antibody drug conjugates using gas chromatography.
abstract: The detection and quantification of residual solvents present in clinical and commercial pharmaceutical products is necessary from both patient safety and regulatory perspectives. Head-space gas chromatography is routinely used for quantitation of residual solvents for small molecule APIs produced through synthetic processes; however residual solvent analysis is generally not needed for protein based pharmaceuticals produced through cultured cell lines where solvents are not introduced. In contrast, antibody drug conjugates and other protein conjugates where a drug or other molecule is covalently bound to a protein typically use solvents such as N,N-dimethylacetamide (DMA), N,N‑dimethylformamide (DMF), dimethyl sulfoxide (DMSO), or propylene glycol (PG) to dissolve the hydrophobic small molecule drug for conjugation to the protein. The levels of the solvent remaining following the conjugation step are therefore important to patient safety as these parental drug products are introduced directly into the patients bloodstream. We have developed a rapid sample preparation followed by a gas chromatography separation for the detection and quantification of several solvents typically used in these conjugation reactions. This generic method has been validated and can be easily implemented for use in quality control testing for clinical or commercial bioconjugated products.
authors.affiliation: Genentech Inc., Small Molecule Pharmaceutical Sciences, 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: medley.colin@gene.com.
authors.forename: Colin D
authors.initials: CD
authors.lastname: Medley
authors.affiliation: Research Pharmaceutical Services, 520 Virginia Dr. Fort, Washington, PA, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Kay
authors.affiliation: Genentech Inc., Small Molecule Pharmaceutical Sciences, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Genentech Inc., Small Molecule Pharmaceutical Sciences, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Gruenhagen
authors.affiliation: Genentech Inc., Small Molecule Pharmaceutical Sciences, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Yehl
authors.affiliation: Genentech Inc., Small Molecule Pharmaceutical Sciences, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Nik P
authors.initials: NP
authors.lastname: Chetwyn
mesh_terms: D002849:Chromatography, Gas / Q000379:methods*; D004340:Drug Contamination; D018796:Immunoconjugates / Q000737:chemistry*; D012997:Solvents / Q000302:isolation & purification*
chemical_list: D018796:Immunoconjugates; D012997:Solvents
keywords: Antibody drug conjugate; Gas chromatography; Pharmaceutical analysis; Residual solvents