ABSTRACT
Identification of low levels of a metabolite of unaltered skeletal structure, 1-chloro-3-ethynylpent-1-en-3,4-diol (VII), detected in biological specimens of both nonfatal and fatal poisonings with DL-1-chloro-3-ethylpent-1-en-4-yn-3-ol (ethchlorvynol, la), has been achieved by high-resolution GC/MS. Corroborative evidence for the assigned structure (VII) was provided by synthesis, the design of which included as a central objective, concurrent access to 1-chloro-3-ethynyl-3,4-epoxy-1-pentene (VI), the putative direct precursor of VII. The diastereomeric epoxide mixture (VI) is mutagenic toward Escherichia coli WP2 try-hcr-, a UV-deficient repair strain. By contrast, neither Ia, VI, nor VII proved to be mutagenic toward Salmonella typhimurium (TA98, TA100, TA1535, and TA1539) with or without a liver postmitochondrial fraction. However, the epoxides (VI) proved cytotoxic to, for example, TA100, which apparently overlies its potency as a mutagen. The cytotoxicity of VI was also apparent in an in vitro culture system.
Subject(s)
Ethchlorvynol/metabolism , Cell Division/drug effects , Chemical Phenomena , Chemistry , Ethchlorvynol/adverse effects , Humans , Mutagens , Salmonella typhimurium/drug effectsABSTRACT
A GLC analysis for free ftorafur was developed to follow in drug disposition in body fluids of patients. The free drug was extracted from aqueous biological samples with chloroform, derivatized by methylation, and chromatographed on 1% HI-EFF 8BP using flame-ionization detection. The analysis is sensitive (0.25 microgram/ml of plasma) and specific for the intact molecule, and it does not interfere with subsequent fluorouracil analysis of the same sample.
Subject(s)
Fluorouracil/analogs & derivatives , Tegafur/analysis , Chromatography, Gas , Drug Stability , Fluorouracil/blood , Humans , Methods , Tegafur/blood , Time FactorsABSTRACT
A feasibility demonstration with a gas chromatograph/mass spectrometer/computer system (GC/MS) was initiated to provide a 24-hour (seven days/week) adjunct emergency toxicology service to the hospitals in the tricounty area comprising Metropolitan Detroit. During June 1, 1974, to April 1, 1975, more than 85 different drugs and other agents were identified in the body fluids of approximately 1,000 victims of accidental or deliberate poisonings. At least one toxic substance was identified in 57% of the cases, and the presence of two or more drugs was established in one of five (19%) of the victims. This study indicates that a centrally located GC/MS/computer system can provide an effective adjunct emergency toxicology service for an entire metropolitan community and thereby provide guidelines for a prompt and rational therapy.
