Reichardt's dye and its reactions with the alkylating agents 4-chloro-1-butanol, ethyl methanesulfonate, 1-bromobutane and Fast Red B - a potentially useful reagent for the detection of genotoxic impurities in pharmaceuticals

Damion K. Corrigan, Michael J. Whitcombe, Sean McCrossen, Sergey Piletsky

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objectives 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.

Methods 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.

Key findings 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.

Conclusions 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.
LanguageEnglish
Pages533-537
Number of pages5
JournalJournal of Pharmacy and Pharmacology
Volume61
Issue number4
DOIs
Publication statusPublished - 2009

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Ethyl Methanesulfonate
Alkylating Agents
Alkylation
Pharmaceutical Preparations
Coloring Agents
Dimethylformamide
Acetaminophen
High Pressure Liquid Chromatography
Fast Red B
2,6-diphenyl-4-(2,4,6-triphenyl-1-pyridinio)phenolate
4-chloro-1-butanol
butyl bromide

Keywords

  • Reichardt's dye
  • genotoxic impurities
  • alkylating agents
  • UV absorption

Cite this

@article{5f88d08f026f4744ac44fdff1e6b1a0c,
title = "Reichardt's dye and its reactions with the alkylating agents 4-chloro-1-butanol, ethyl methanesulfonate, 1-bromobutane and Fast Red B - a potentially useful reagent for the detection of genotoxic impurities in pharmaceuticals",
abstract = "Objectives 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.Methods 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.Key findings 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.Conclusions 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.",
keywords = "Reichardt's dye, genotoxic impurities, alkylating agents, UV absorption",
author = "Corrigan, {Damion K.} and Whitcombe, {Michael J.} and Sean McCrossen and Sergey Piletsky",
year = "2009",
doi = "10.1211/jpp.61.04.0017",
language = "English",
volume = "61",
pages = "533--537",
journal = "Journal of Pharmacy and Pharmacology",
issn = "0022-3573",
number = "4",

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TY - JOUR

T1 - Reichardt's dye and its reactions with the alkylating agents 4-chloro-1-butanol, ethyl methanesulfonate, 1-bromobutane and Fast Red B - a potentially useful reagent for the detection of genotoxic impurities in pharmaceuticals

AU - Corrigan, Damion K.

AU - Whitcombe, Michael J.

AU - McCrossen, Sean

AU - Piletsky, Sergey

PY - 2009

Y1 - 2009

N2 - Objectives 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.Methods 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.Key findings 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.Conclusions 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.

AB - Objectives 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.Methods 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.Key findings 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.Conclusions 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.

KW - Reichardt's dye

KW - genotoxic impurities

KW - alkylating agents

KW - UV absorption

U2 - 10.1211/jpp.61.04.0017

DO - 10.1211/jpp.61.04.0017

M3 - Article

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EP - 537

JO - Journal of Pharmacy and Pharmacology

T2 - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

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ER -