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Atmospheric Pressure Ionization (atmospheric + pressure_ionization)
Selected AbstractsAtmospheric pressure desorption/ionization on silicon ion trap mass spectrometry applied to the quantitation of midazolam in rat plasma and determination of midazolam 1,-hydroxylation kinetics in human liver microsomesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 24 2006Rick C. Steenwyk The application of atmospheric pressure desorption/ionization on silicon (AP-DIOS) coupled with ion trap mass spectrometry (ITMS) was investigated for the quantification of midazolam in rat plasma, and determination of midazolam 1,-hydroxylation kinetics in pooled human liver microsomes. Results indicate good sensitivity with absolute detection limits for midazolam in rat plasma of approximately 300 femtograms. A linear dynamic range from approximately 10,5000,ng/mL was obtained in rat plasma with analysis times of 1,min per sample. Kinetic constants for midazolam 1,-hydroxylation in human liver microsomes yielded an apparent Km of 10.0,µM and Vmax of 6.4,nmol/min/mg. Studies investigating the inhibition of 1,-hydroxymidazolam formation by the cytochrome P450 3A4 model inhibitor ketoconazole yielded an IC50 of 0.03,µM. Quantitative precision for replicate analysis of rat plasma and human liver microsomal samples was variable with relative standard deviation (RSD) values ranging from a low of approximately 3% to over 50%, with the highest variability observed in data from human liver microsomal incubations. While preliminary studies investigating the application of AP-DIOS-ITMS suggested feasibility of this technique to typical pharmacokinetic applications, further work is required to understand the underlying causes for the high variability observed in these investigations. Copyright © 2006 John Wiley & Sons, Ltd. [source] Determination of linear response in the detection of mixtures of aroma compounds by atmospheric pressure ionization,mass spectrometry (API,MS)FLAVOUR AND FRAGRANCE JOURNAL, Issue 1 2008Roberto A. Buffo Abstract The linearity of atmospheric pressure ionization,mass spectrometry (API,MS) response in mixtures of aroma compounds was determined for a ,homogeneous' system (four esters) and a ,heterogeneous' system (five compounds of different chemical functionality). All combinations analysed within each system followed a saturation pattern as concentration increased. Total linear responses were determined by the linear behaviour of individual compounds. Ionization patterns within each mixture were explained by proton affinity data (i.e. the species' ability to accept protons), molecular reaction rates (defined by molecular weight), and product ion distribution (according to fragmentation of the corresponding parent ion). Copyright © 2007 John Wiley & Sons, Ltd. [source] Distinguishing N -oxide and hydroxyl compounds: impact of heated capillary/heated ion transfer tube in inducing atmospheric pressure ionization source decompositionsJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 6 2004Dilrukshi M. Peiris Abstract In the pharmaceutical industry, a higher attrition rate during the drug discovery process means a lower drug failure rate in the later stages. This translates into shorter drug development time and reduced cost for bringing a drug to market. Over the past few years, analytical strategies based on liquid chromatography/mass spectrometry (LC/MS) have gone through revolutionary changes and presently accommodate most of the needs of the pharmaceutical industry. Among these LC/MS techniques, collision induced dissociation (CID) or tandem mass spectrometry (MS/MS and MSn) techniques have been widely used to identify unknown compounds and characterize metabolites. MS/MS methods are generally ineffective for distinguishing isomeric compounds such as metabolites involving oxygenation of carbon or nitrogen atoms. Most recently, atmospheric pressure ionization (API) source decomposition methods have been shown to aid in the mass spectral distinction of isomeric oxygenated (N -oxide vs hydroxyl) products/metabolites. In previous studies, experiments were conducted using mass spectrometers equipped with a heated capillary interface between the mass analyzer and the ionization source. In the present study, we investigated the impact of the length of a heated capillary or heated ion transfer tube (a newer version of the heated capillary designed for accommodating orthogonal API source design) in inducing for-API source deoxygenation that allows the distinction of N -oxide from hydroxyl compounds. 8-Hydroxyquinoline (HO-Q), quinoline- N -oxide (Q-NO) and 8-hydroxyquinoline- N -oxide (HO-Q-NO) were used as model compounds on three different mass spectrometers (LCQ Deca, LCQ Advantage and TSQ Quantum). Irrespective of heated capillary or ion transfer tube length, N -oxides from this class of compounds underwent predominantly deoxygenation decomposition under atmospheric pressure chemical ionization conditions and the abundance of the diagnostic [M + H , O]+ ions increased with increasing vaporizer temperature. Furthermore, the results suggest that in API source decompostion methods described in this paper can be conducted using mass spectrometers with non-heated capillary or ion transfer tube API interfaces. Because N-oxides can undergo in-source decomposition and interfere with quantitation experiments, particular attention should be paid when developing API based bioanalytical methods. Copyright © 2004 John Wiley & Sons, Ltd. [source] Analytical strategies for identifying drug metabolitesMASS SPECTROMETRY REVIEWS, Issue 3 2007Chandra Prakash Abstract With the dramatic increase in the number of new chemical entities (NCEs) arising from combinatorial chemistry and modern high-throughput bioassays, novel bioanalytical techniques are required for the rapid determination of the metabolic stability and metabolites of these NCEs. Knowledge of the metabolic site(s) of the NCEs in early drug discovery is essential for selecting compounds with favorable pharmacokinetic credentials and aiding medicinal chemists in modifying metabolic "soft spots". In development, elucidation of biotransformation pathways of a drug candidate by identifying its circulatory and excretory metabolites is vitally important to understand its physiological effects. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) have played an invaluable role in the structural characterization and quantification of drug metabolites. Indeed, liquid chromatography (LC) coupled with atmospheric pressure ionization (API) MS has now become the most powerful tool for the rapid detection, structure elucidation, and quantification of drug-derived material within various biological fluids. Often, however, MS alone is insufficient to identify the exact position of oxidation, to differentiate isomers, or to provide the precise structure of unusual and/or unstable metabolites. In addition, an excess of endogenous material in biological samples often suppress the ionization of drug-related material complicating metabolite identification by MS. In these cases, multiple analytical and wet chemistry techniques, such as LC-NMR, enzymatic hydrolysis, chemical derivatization, and hydrogen/deuterium-exchange (H/D-exchange) combined with MS are used to characterize the novel and isomeric metabolites of drug candidates. This review describes sample preparation and introduction strategies to minimize ion suppression by biological matrices for metabolite identification studies, the application of various LC-tandem MS (LC-MS/MS) techniques for the rapid quantification and identification of drug metabolites, and future trends in this field. © 2007 Wiley Periodicals, Inc., Mass Spec Rev [source] Electrospray ionization mass spectrometric characterization and quantitation of xanthine derivatives using isotopically labelled analogues: an application for equine doping control analysisRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 14 2004Mario Thevis Isotope-dilution mass spectrometry has been employed successfully in numerous fields of analytical chemistry enabling the establishment of fast and reliable procedures. In equine sports, xanthine derivatives such as caffeine and theobromine are prohibited, and doping control laboratories analyze horse urine specimens regarding these illicit performance-enhancing drugs. Theobromine has to exceed a threshold level of 2,,g/mL, hence a robust and reliable quantitation is required. Stably deuterated theobromine and caffeine were synthesized by the reaction of xanthine or theobromine with iodomethane-d3 in the presence of N -methyl- N -trimethylsilyltrifluoroacetamide or potassium carbonate in acetonitrile, respectively. Both compounds were characterized by nuclear magnetic resonance spectroscopy and electrospray ionization tandem mass spectrometry, and a robust and fast assay for the qualitative and quantitative analysis of theobromine in equine urine samples was validated. Urine specimens were extracted by means of solid-phase extraction cartridges, and concentrated extracts were analyzed by liquid chromatography interfaced to a triple-quadrupole mass spectrometer. In addition, the dissociation behavior of deuterated analogues to caffeine and theobromine allowed proposals for fragmentation routes of xanthine derivatives after atmospheric pressure ionization and collisionally activated dissociation. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||