A novel four- channel multiplexed electrospray liquid chromatography interface is described. This device has been used to analyse both single components and mixtures by liquid chromatography/mass spectrometry (LC/MS) as well as synthetic samples prepared by automated procedures. These data provided unambiguous molecular weight assignments to both major components and synthetic by-products in these samples. In this work particular attention has also been paid to the elimination of interchannel crosstalk. Copyright 1999 John Wiley & Sons, Ltd.

Electrospray ionisation mass spectrometry has been used to show that the synthetic 40 ammo acid /7-amyloid peptide @140) interacts with the cyclic oligosaccharide/?-cyclodextrin. This interaction, presumably with the hydrophobic aromatic moieties on the peptide, has been shown to diminish substantially the neurotoxic effects of /340 in a cell line.

This paper describes the use of two separate electrosprays for introducing sample and reference for accurate mass liquid chromatography/mass spectrometry (LC/MS) on an orthogonal acceleration time-of-flight mass analyzer. This is carried out using an adaptation of the multiplexed electrospray ion source in which only two of the sprays are utilized. Results are shown for the positive ion detection of trace-level components in complex matrixes and good mass accuracies are obtained, even for very low level components. An example of accurate mass measurements obtained using negative ion LC/MS is also shown. To obtain additional structural information, an example of cone voltage fragmentation is included and shows that good mass accuracy can be obtained for both precursor and fragment ions.

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 resolution capabilities of the ToF analyser allow accurate mass measurement of the fragment ions to better than 5 ppm in most cases.

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The formation of non-covalently bound inclusion complexes between p-cyclodextrin and peptides containing aromatic acid residues has been confirmed by electrospray ionization mass spectrometry. This preliminary study has indicated that phenylalanine and tryptophan residues can form 1 : 1 complexes with fi-cyclodextrin whereas no evidence for such a complex could be found for tyrosine residues. Bradykinin, which contains two phenylalanine residues, formed both 1 : 1 and 1 : 2 complexes.6-Cyclodextrin (p-CD) is a cyclic oligosaccharide consisting of seven glucopyranose units. The 'torus'-shaped structure of this molecule has seven primary and fourteen secondary hydroxyl groups located at the narrower entrance and the wider entrance, respectively. The presence of these hydroxy groups makes the outer surface of 0-CD hydrophilic, whereas the hydrocarbon structure of the interior of the 'torus' renders the cavity lipophilic in nature.The hydrophobic interaction between p-CD and a number of aromatic moieties in aqueous solution leads to the formation of inclusion complexes. 1-3 Besides its hydrophobicity, the size of the 'guest' molecule relative to that of the p-CD cavity is an important factor in determining the extent of the non-covalent interaction. A number of molecules containing phenyl, naphthyl, or other aromatic groups of comparable size, form, in the majority of cases, 1 : 1 inclusion complexes. Studies on these 'host-guest' complexes in solution have utilized physico-chemical techni ues such as nuclear magnetic resonance spectroscopyp4 spectrofluorimetry? circular dichroism5 and mass spectrometry.6 In the solid form, the ability of j3-CD to include aromatic moieties has been confirmed by X-ray crystallography.' p-CD and related cyclic oligosaccharides have been reported to interact with peptides and proteins through the formation of inclusion complexes with aromatic amino acids, in particular, phenylalanine, tyrosine and tryptophan.', The occurrence of these complexes has been inferred from observations of significant improvement in the solubility and stabilization of these proteins in the presence of cyclodextrins. In this Communication we report the use of electrospray ionization mass spectrometry (ESI-MS) to study the interaction of p-CD with phenylalanine, tyrosine, tryptophan and some peptides containing one or more of these amino acid residues. The utility of this relatively 'soft' ionization technique for the study of the noncovalently bound complexes has been demonstrated recently by several ESI-MS analysis was performed on a Vestec 201 mass spectrometer (Vestec Corp., Texas, USA). Compounds were dissolved in a solvent mixture made up of water saturated with p-CD (about 0.185g/L,

We outline simple methodology for the rapid and selective analysis of 2-aminoacridone (2-AMAC) derivatised oligosaccharides by matrix-assisted laser desorption/ionization mass spectrometry. This involves the addition of small amounts of lithium chloride to the matrix before evaporation of solvent and crystallization. Signals mainly attributed to proton, sodium and potassium adducts are suppressed to a great extent, and a single signal due to (M + Li)+ is observed. This technique is rapid and is most useful for the direct analysis of complex glycan mixtures, after derivatization with 2-aminoacridone and without separation of the individual components.

Electrospray mass spectrometry has been used to study the complexation of 'guest' molecules with a mixture of hydroxypropyl-substituted @-cyclodextrin derivatives. In all cases studied, the predominant derivative was shown to contain a maximum of seven hydroxypropyl groups, most probably related to alkylation of each of the seven glucose units of the parent @-cyclodextrin. Chiral selectivity was not observed for D-and L-phenylalanine methyl esters. In contrast D-propranolol and L-tryptophan methyl ester formed stronger complexes than the corresponding L-and o-enantiomers, respectively. Molecular modelling studies were also carried out, in an attempt to identify the factors that can play a part in determining the mechanism of the observed non-covalent interactions.a-, p-, and y-Cyclodextrins are cyclic amylases made up of six, seven, or eight a-1,4-linked D-glucose pyranose units, respectively. These molecules, in particular p-