Premium
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
Author(s) -
Louw Stefan,
Njoroge Mathew,
ChigorimboMurefu Nyaradzo,
Chibale Kelly
Publication year - 2012
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.6359
Subject(s) - chemistry , atmospheric pressure chemical ionization , mass spectrometry , chromatography , fragmentation (computing) , electrospray ionization , ammonium formate , adulterant , high performance liquid chromatography , dihydroartemisinin , artemisinin , electrospray , analytical chemistry (journal) , triple quadrupole mass spectrometer , chemical ionization , ionization , selected reaction monitoring , tandem mass spectrometry , ion , organic chemistry , malaria , computer science , immunology , plasmodium falciparum , biology , operating system
RATIONALE 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. Copyright © 2012 John Wiley & Sons, Ltd.