A study of the analytical behaviour of selected new molecular entities using electrospray ionisation ion trap mass spectrometry, liquid chromatography, gas chromatography and polarography and their determination in serum at therapeutic concentrations.
This paper provides analytical chemical information on selected new molecular entities (NMEs) which are drugs that have recently been approved by the FDA. These are the antiretroviral drugs, atazanavir, indinavir and emtricitabine, the antibacterial gemifloxacin, rosuvastatine which is a cholesterol-lowering drug, the anti-cancer drug gefitinib and aprepitant for neurological disorders. Electrospray ionisation-quadrupole ion trap mass spectrometry (ESI-MS(n)) was employed to generate tandem mass spectrometric (MS(2)) data of the drugs studied and structural assignments of product ions were supported by quadrupole time-of-flight mass spectrometry (QToF-MS/MS). These fragmentation studies were then utilised in the development and validation of a specific and sensitive liquid chromatographic method (LC-ESI-MS(2)) to identify and determine these drugs at therapeutic concentration levels in serum after a single protein precipitation procedure with acetonitrile. In addition, this method was compared to the application of gas liquid chromatography-flame ionisation detection (GLC-FID) and differential pulse polarography (DPP) for the analysis of these NMEs in serum.
Rodríguez Robledo
Virginia
V
Department of Analytical Chemistry and Food Technology, University of Castilla-La Mancha, Ciudad Real, Spain.
Smyth
W Franklin
WF
D000097:Acetonitriles / Q000737:chemistry; D011232:Chemical Precipitation; D002849:Chromatography, Gas / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods*; D004358:Drug Therapy; D005410:Flame Ionization; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000097:blood* / Q000737:chemistry* / Q000378:metabolism; D011048:Polarography / Q000379:methods*; D011506:Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D000097:Acetonitriles; D006573:Heterocyclic Compounds, 1-Ring; D004364:Pharmaceutical Preparations; D011506:Proteins