Analytical controls in drug metabolic studies. II. Artifact formation during chloroform extraction of drugs and metabolites with amine substituents

E. J. Cone, W. F. Buchwald, W. D. Darwin

Research output: Contribution to journalArticlepeer-review

Abstract

Chemical artifacts are readily produced during chloroform extractions of drugs and metabolites with amine substituents by the reaction of chloroform contaminants, phosgene and ethyl chloroformate, to form carbamoyl chlorides and carbamates. Chloroform obtained from three different supplies was examined with regard to the effects of preservatives and exposure to air on the quantity and nature of these contaminants. Extractions with chloroform obtained from a supplier's sealed bottle and containing ethanol preservative produced the least amount of artifact. With previously opened bottles (prior exposure to air, open), the amount of artifact formation rose substantially. Chloroform without preservation or with a nonpolar hydrocarbon preservative likewise produced large amounts of artifacts during extraction. Attempts to purify chloroform showed that distillation was ineffective for the removal of phosgene or ethyl chloroformate, whereas their effective removal was accomplished by solvent elution through a column of activated alumina or upon standing over calcium hydroxide powder. Possible artifact formation must be considered in drug-metabolism studies and appropriate controls included for the detection and elimination of chemical artifacts.

Original languageEnglish (US)
Pages (from-to)561-567
Number of pages7
JournalDrug Metabolism and Disposition
Volume10
Issue number6
StatePublished - Dec 1 1982

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Fingerprint

Dive into the research topics of 'Analytical controls in drug metabolic studies. II. Artifact formation during chloroform extraction of drugs and metabolites with amine substituents'. Together they form a unique fingerprint.

Cite this