|SOFT - TIAFT 1998||Poster Session 4||Friday October 9, 1998|
SENSITIVITY LIMITS OF LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY (LC-MS/MS) IN TOXICOLOGY APPLICATIONS PERFORMED WITH AN ION TRAP|
Th. Y. Gougnard, C. J. Charlier, G. J. Plomteux
Laboratory of Clinical Toxicology, C.H.U. de Liège, B-4000 Sart Tilman, Belgium
|A major application of LC-MS/MS in toxicology is the determination of small drug molecules and their metabolites in body fluid matrices. Using the MS/MS and MSn capabilities of ion trap technology significantly improves the selectivity and specificity for those samples in crude mixtures. As well, LC-MS/MS reduces often also the requirements for sample preparation and purification. The requirements for the LC separation are greatly reduced, i.e. a time consuming chromatography can be avoided in many cases. Finally, the sensitivity limits are usually lower than those of the UV detection in HPLC or classical mass spectrometers used in toxicology.
In this report, results on the determination of plasma neuroleptics and some investigations into the limits of detection of compounds difficult to identify like buprenorphine, LSD and pancuronium will be presented.
Neuroleptics represent a very heterogenous pharmacological group of drugs (phenothiazines, thioxanthenes, butyrophenones, etc) with a wide range of therapeutic and toxic concentrations (from ng/ml up to µg/ml). They are frequently used in suicide attempts but all existing systematic toxicological analysis procedures are just sensitive enough to find only the most concentrated ones (i.e. chlorpromazine, prothipendyl). More sensitive methods are generally focused on one specific compound like haloperidol or benperidol. Using liquid chromatography coupled with an ion trap mass spectrometry detector, we have developed a method to screen and identify the most relevant compounds in plasma. After a classical screening extraction procedure with Bond Elut Certify SPE column, 5 µl of the extract were injected into a C18 HPLC column (Phenomenex Jupiter 50 x 2.0 mm i.d.). Separation of neuroleptics was achieved with a mobile phase 2 mM formic acid pH 3.5/acetonitrile (50/50 ; v/v) at 0.5 ml/min. With multiple reactions monitoring (MRM), specific mass transitions allowed the identification of twelve of the most relevant neuroleptics. Limits of detection varied from 0.1 to 1 ng/ml depending on the drug.