2-6-diphenyl-4-(2-4-6-triphenyl-1-pyridinio)phenolate and butyl-bromide

Alkylating agents are potentially genotoxic impurities that may be present in drug products. These impurities occur in pharmaceuticals as by-products from the synthetic steps involved in drug production, as impurities in starting materials or from in-situ reactions that take place in the final drug product. Currently, analysis for genotoxic impurities is typically carried out using either HPLC/MS or GC/MS. These techniques require specialist expertise, have long analysis times and often use sample clean-up procedures. Reichardt's dye is well known for its solvatochromic properties. In this paper the dye's ability to undergo alkylation is reported.. The reaction between Reichardt's dye and alkylating agents such as 4-chloro-1-butanol and ethyl methanesulfonate was monitored spectrophotometrically at 618 nm in acetonitrile and 624 nm in N,N-dimethylformamide.. Changes in absorption were observed using low levels of alkylating agent (5-10 parts per million). Alkylation of the dye with 4-chloro-1-butanol and ethyl methanesulfonate was confirmed. Reichardt's dye, and its changing UV absorption, was examined in the presence of paracetamol (10 and 100 mg/ml). Whilst the alkylation-induced changes in UV absorption were not as pronounced as with standard solutions, detection of alkylation was still possible.. Using standard solutions and in the presence of a drug matrix, Reichardt's dye shows promise as a reagent for detection of low levels of industrially important alkylating agents.

Topics: Alkylating Agents; Chemistry, Pharmaceutical; Chlorobutanol; Chromogenic Compounds; Diazonium Compounds; Drug Contamination; Ethyl Methanesulfonate; Hydrocarbons, Brominated; In Vitro Techniques; Magnetic Resonance Spectroscopy; Mutagens; Pyridinium Compounds