title: Comparison of electrospray ionisation, atmospheric pressure chemical ionisation and atmospheric pressure photoionisation for the identification of metabolites from labile artemisinin-based anti-malarial drugs using a QTRAP® mass spectrometer.
abstract: BACKGROUND
  Artemisinin-based drugs and their metabolites are prone to in-source fragmentation under atmospheric pressure ionisation mass spectrometry (API-MS) conditions. To facilitate correct and efficient identification of all possible drug metabolites using full scan MS analyzer methods, stable [M + NH(4) ](+) ions should be produced in the MS source.
  
  
  METHODS
  Using a high-performance liquid chromatography (HPLC) hybrid triple quadrupole linear ion trap MS system, electrospray ionisation (ESI), atmospheric pressure chemical ionisation (APCI) and atmospheric pressure photoionisation (APPI) methods were developed for the detection of [M + NH(4) ](+) ions of the test compounds dihydroartemisinin, artemisinin, artemether and artesunic acid. The optimised methods employed ammonium formate buffered HPLC mobile phase in combination with moderate source temperatures (100-200 °C) and showed satisfactorily reduced in-source fragmentation.
  
  
  RESULTS
  With a full scan MS analyser method for the detection of the in vitro metabolites of the test compounds, the respective performance of the ESI and APCI methods was found to be comparable. ESI generally resulted in less in-source fragmentation. Incorrect assignment of metabolites resulted from strong in-source fragmentation of artemether using the APPI method. The most number of metabolites could be detected using ESI in combination with a selective MS analyser method.
  
  
  CONCLUSIONS
  ESI and APCI full scan methods proved to be capable of detecting any drug metabolites present in reasonable concentrations, and are useful when employed in addition to selective scan methods that target low level expected metabolites. APPI can be a valuable alternative for detecting expected metabolites due to good signal-to-noise (S/N) ratio.
authors.affiliation: Department of Chemistry and Institute of Infectious Disease & Molecular Medicine, University of Cape Town, Rondebosch, 7701, South Africa.
authors.forename: Stefan
authors.initials: S
authors.lastname: Louw
authors.forename: Mathew
authors.initials: M
authors.lastname: Njoroge
authors.forename: Nyaradzo
authors.initials: N
authors.lastname: Chigorimbo-Murefu
authors.forename: Kelly
authors.initials: K
authors.lastname: Chibale
mesh_terms: D000962:Antimalarials / Q000032:analysis / Q000378:metabolism*; D037621:Artemisinins / Q000032:analysis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008862:Microsomes, Liver / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: D000962:Antimalarials; D037621:Artemisinins