Screening for drugs in serum by electrospray ionization/collision-induced dissociation and library searching

Factors influencing in-source collision-induced dissociation (ESI/CID) of o rganic molecules in a Perkin-Elmer/SCIEX ionspray source have been investig ated. Breakdown curves of four drugs and organic compounds were acquired by monitoring the intensities of MH+ and specific fragment ions while ramping the orifice voltage. Haloperidol, diazepam, 1,4-acetamido-acetoxybenzene a nd diacetamido-1,2-benzene were found to be substances with characteristic breakdown curves, with maximums and points of intersection at orifice volta ges between 20 and 70 V. The breakdown curves of haloperidol were used for comparison of ESI/CID with ionspray and turboionspray sources on three PE/S CIEX-API instruments. Using standardized source parameters and mass resolut ion, very similar fragmentation graphs were obtained for haloperidol with a ll instruments. Infusion of varying concentrations of haloperidol (0.1 to 1 0 mu g/mL with ionspray and 0.01 to 1 mu g/mL with turboionspray) yielded c omparable breakdown curves. With turboionspray, a preconcentration of the a erosol occurred, yielding higher ion abundances. Solvent pH and the ratio o f aqueous ammonium formate/acetonitrile had minor effects on the degree of fragmentation of haloperidol in a wide range. With these preconditions, a c urrently expanding mass spectral library of 400 drugs was set up by liquid chromatography/mass spectrometry with alternating orifice voltages (20, 50, and 80 V, respectively) in a looped experiment. An example of drug identif ication in a patient's serum with Library search is shown. (J Am Soc Mass S pectrom 1999, 10, 1028-1037) (C) 1999 American Society for Mass Spectrometr y.