Drug impurity profiling by capillary electrophoresis/mass spectrometry using various ionization techniques

P. Hommerson, A.M. Khan, T. Bristow, M.W. Harrison, G.J. de Jong, G.W. Somsen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Capillary electrophoresis/mass spectrometry (CE/MS) is predominantly carried out using electrospray ionization (ESI). Recently, atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) have become available for CE/MS. With the VUV lamp turned off, the APPI source may also be used for CE/MS by thermospray ionization (TSI). In the present study the suitability of ESI, APCI, APPI and TSI for drug impurity profiling by CE/MS in the positive ion mode is evaluated. The drugs carbachol, lidocaine and proguanil and their potential impurities were used as test compounds, representing different molecular polarities. A background electrolyte of 100 mM acetic acid (pH 4.5) provided baseline separation of nearly all impurities from the respective drugs. APPI yielded both even- and odd-electron ions, whereas the other ionization techniques produced even-electron ions only. In-source fragmentation was more pronounced with APCI and APPI than with ESI and TSI, which was most obvious for proguanil and its impurities. In general, ESI and TSI appeared the most efficient ionization techniques for impurities that are charged in solution achieving detection limits of 100 ng/mL (full-scan mode). APPI and APCI showed a lower efficiency, but allowed ionization of low and high polarity analytes, although quaternary ammonium compounds (e.g. carbachol) could not be detected. Largely neutral compounds, such as the lidocaine impurity 2,6-dimethylaniline, could not be detected by TSI, and yielded similar detection limits (500 ng/mL) for ESI, APPI and APCI. In many cases, impurity detection at the 0.1% (w/w) level was possible when 1 mg/mL of parent drug was injected with at least one of the CE/MS systems. Overall, the tested CE/MS systems provide complementary information as illustrated by the detection and identification of an unknown impurity in carbachol. Copyright (C) 2009 John Wiley & Sons, Ltd.
Original languageUndefined/Unknown
Pages (from-to)2878-2884
Number of pages7
JournalRapid Communications in Mass Spectrometry
Volume23
Issue number18
Publication statusPublished - 2009

Keywords

  • Farmacie/Biofarmaceutische wetenschappen (FARM)
  • Medical technology
  • Farmacie(FARM)
  • Bescherming en bevordering van de menselijke gezondheid
  • Biomedische technologie en medicijnen
  • Public Health
  • Analytical chemistry
  • Drugmisbruik en verslaving

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