In-source CID mass spectral libraries for the "general unknown" screening of drugs and toxicants

A "general unknown" screening procedure for drugs and toxicants using LC-ES-MS was developed. It involved in-source collision induced dissociation of the molecular ions (in the negative-ion mode) or protonated molecules (in the positive-ion mode) generally obtained from electrospray sources. Spectra were reconstructed by adding, on one hand, a pair of positive spectra, one without and one with fragmentation, and on the other a pair of negative spectra acquired in similar conditions. These reconstructed spectra showed at least as many fragments as MS/MS spectra, and sometimes as many as electron-ionisation spectra. They were repeatable and reproducible enough to be used for the specific identification of hundreds of molecules. Libraries of about 1100 positive spectra and 500 negative spectra were constructed and are used routinely, together with chromatographic separation involving a Nucleosil C18, 5 mum column (150 x 1 mm i.d.) and a gradient of acetonitrile in 2 mM, pH 3 ammonium formate as a screening technique complementary to GC-MS and HPLC-DAD.