OPTIMIZATION AND APPLICATION OF PARTICLE BEAM HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY MASS-SPECTROMETRY TO COMPOUNDS OF PHARMACEUTICAL INTEREST

Particle beam high‐performance liquid chromatography/mass spectrometry (HPLC/MS) parameters were optimized for the sensitive analysis of several drugs in agricultural products such as milk and tissue. Sensitivity of the particle beam interface was greatest for solvents with low heat capacities (methanol > acetonitrile > isopropanol > water). Furthermore, optimal sensitivity was obtained at low solvent flow rates (about 0.4–0.6 ml min−1). Parameters such as desolvation temperature, helium flow rate to the nebulizer and nebulizer position resulted in minimal change in sensitivity. The source temperature was optimized to obtain suitable vaporization with minimal thermal degradation (200–300 °C). The determination of a variety of compounds (including β‐lactams, cephapirin, tetracyclines, methylene blue, furosemide, spectinomycin, cytidine, 2‐chloro‐4‐nitrobenzamide and thiamine) was possible using the particle beam interface. Under full‐scan conditions, detection limits were in the 100 ng range for most drugs. With selected ion monitoring, particle beam HPLC/MS was demonstrated for the analysis of p.p.m. levels of these drugs in milk and tissue extracts. Precision of the particle beam analysis was usually better than 15% RSD. For the same compounds, HPLC/MS with a thermospray interface often resulted in less structural information (single ion spectra) then obtained by particle beam with thermospray detection limits varying from 10 ng to 1 μg. Copyright © 1990 John Wiley & Sons, Ltd.