James Ian Langridge

The use of liquid chromatography combined with a quadrupole time‐of‐flight analyser for the identification of trace impurities in drug substance

This paper shows the use of a quadrupole time-of-flight mass spectrometer combined with a liquid chromatograph for the identification of trace impurities in a drug substance. LC/MS/MS data obtained on trace impurities using this instrument compare favourably with those previously obtained on triple quadrupole mass spectrometers and in addition the high resoltuion capabilities of the ToF analyser allow accurate mass measurement of the fragment ions to better than 5 ppm in most cases.

Qualitative and quantitative mass spectrometric analysis of cyclic nucleotides and related enzymes

Abstract The application of fast atom bombardment mass spectrometry (MS) and collisionally induced dissociation with mass-analysed kinetic energy spectrum scanning to biochemical studies of cyclic nucleotides is reviewed. MS analysis of partially purified tissue extracts has enabled the demonstration of the natural occurrence in mammals and higher plants of five cyclic nucleotides in addition to the previously established adenosine 3′,5′-cyclic monophosphate; analysis of the products of a putative cytidylate cyclase enzyme-catalyzed reaction has demonstrated the biosynthesis of cytidine 3′,5′-cyclic monophosphate and four novel analogues as side products, thereby enabling the development of specific assays. Quantitative applications have included kinetic analysis of phosphodiesterase and cyclic nucleotide-responsive protein kinase activity, while further quantitative applications have included the structural elucidation of synthetic cyclic nucleotide derivatives used in pharmacological studies. The impact of MS upon cyclic nucleotide research and its future potential are discussed.

Application of continuous-flow fast atom bombardment mass spectrometry to cyclic nucleotide biochemistry

Abstract The modification and optimization of a continuous-flow fast atom bombardment system for the mass spectrometric analysis of cyclic nucleotides is described. The most effective solvent matrix was water-methanol-glycerol (70: 20: 10, v/v/v) and the optimum probe tip operating temperature was 40 °C. Modification of the probe tip was necessary to facilitate solvent evaporation and a solvent degassing and filter system were found to be essential. Comparison of the theoretical sensitivies of the continuous and static systems with cytidine 3′,5′-cyclic monophosphate as analyte indicated a increase of between one and two orders of magnitude, with a significant increase in signal-to-noise ratio also observed. Analysis of sample mixtures simulating enzyme incubates has proved successful and the potential application of dynamic fast atom bombardment systems in quantitative analysis of enzymes is further discussed here.

QUALITATIVE AND QUANTITATIVE ANALYSIS OF CYCLIC NUCLEOTIDES AND RELATED ENZYMES BY STATIC AND DYNAMIC FAST ATOM BOMBARDMENT MASS SPECTROMETRY

Abstract Fast atom bombardment mass spectrometry in concert with collisionally-induced dissociation and mass-analysed kinetic energy spectrum scanning has enabled unequivocal identification of putative cyclic nucleotides in tissue extracts; quantitative analyses have enabled kinetic studies of cyclic nucleotide-related enzymes with multi-component monitoring, and dynamic spectrometric systems provide a potential means of continuous assay for these enzymes.