DETERMINATION OF SEDATIVES AND ANESTHETICS IN PLASMA BY LIQUID-CHROMATOGRAPHY MASS-SPECTROMETRY WITH A DESALTING SYSTEM

Though liquid chromatography-mass spectrometry (LC-MS) is a powerful t ool for analysis of drugs and their metabolites, it does not allow the use of a non-volatile buffer such as phosphate buffer. We used a colu mn-switching desalting system in combination with atmospheric pressure chemical ionization LC-MS for analysis of sedatives and anaesthetics. The drugs examined were flumazenil, butorphanol, midazolam, lorazepam , phenobarbital and flunitrazepam. The separation was carried out on a reversed-phase column using acetonitrile-0.1 M phosphate buffer as a mobile phase. The mass spectra are almost the same as those obtained b y direct analysis and the molecular ions were clearly observed. In the analysis, phosphate buffer was completely removed with the trapping c olumn and did not interfere with ionization of the drugs in MS. The ch iral separation of lorazepam was achieved on a chiral column with UV, optical rotatory detection and MS. This method is sufficiently sensiti ve and accurate for the pharmacokinetic studies of these drugs in biol ogical samples. (C) 1998 Elsevier Science B.V.