On-line direct liquid introduction interface for micro-liquid chromatography/mass spectrometry: application to drug analysis.

We describe an integrated micro-liquid chromatograph/mass spectrometer (micro-LC/MS) system capable of performing routine determinations for 1--10 ng of drugs and their metabolites extracted from biological fluids. The micro-LC is constructed from conventional "high-performance" liquid-chromatographic instrumentation by using commercially available components. The mass spectrometer is operated in the chemical ionization mode. The direct liquid introduction micro-LC/MS interface can be constructed from commercially available materials. Chromatographic and mass spectral results demonstrate the ability of the micro-LC and micro-LC/MS system to separate and determine multiple components in standards of trace concentrations and in equine urinary extracts. The stability and sensitivity of this micro-LC/MS system are demonstrated through determinations of trichlormethiazide.