• Optimisation and validation of separation procedures for complex mixtures (quality control of dosage forms) of for closely related compounds (purity testing of active ingredients) by high performance liquid chromatography (HPLC, µ-LC, LC-MS), gaz chromatography (GC), capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC).
• Improvement of detection possibilities in HPLC and CZE by use of the indirect photometric detection method and chemical derivatization techniques (fluorescence, electro-chemistry).
• Optimisation and validation of enantiomeric separations for chiral drugs by use of chiral stationary phases in HPLC and by addition of complexing agents (cyclodextrins, bile acids) to the running buffer in CZE and MEKC.
• Optimisation and validation of fully automated methods for the determination of drugs and active meta-bolites in biological fluids (bioanalysis) by coupling solid phase extraction (SPE) on dis-posable cartridges (ASPEC system), dialysis (ASTED system) or the column swit-ching technique to HPLC and µ-LC.
• Development of knowledge-based systems for the optimisation of automated sample handling in bioanalysis (plasma or serum) by use of the ASPEC and ASTED systems.

The Laboratory of Analytical Pharmaceutical Chemistry has provided services in method development and valida-tion for many years to the Pharmaceutical Industry in the following application areas :

• quality control of dosage forms;
• purity testing of active ingredients;
• stability studies (short and long-term studies on bulk and finished products);
• pharmacokinetic, bioavailability and bioequivalence studies;
• enantiomeric separation of chiral drugs.

The Laboratory of Analytical Pharmaceutical Chemistry is officially approved by the Belgian Ministery of Public Health for the analysis and quality control of pharmaceutical forms and bulk products and its Labora-tory staff members includes two experts of the Belgian and European Pharmaco-poeias. In this respect, the Laboratory of Analytical Pharmaceutical Chemistry participates in the following activities:

• quality control of dosage forms;
• purity testing of active ingredients;
• development of official monographs for the European Pharmacopoeia;
• national and international collaborative studies;
• European network of official medecine control laboratories.

In addition, the Analytical Pharmaceutical Chemistry Laboratory offers the following services :

• consultancy and expert's reports;
• preparation of dossiers for new drug application (regulatory affairs);
• educational training : theoretical and practical courses (Validation '93, '94 and ´98);
• organization of national and international congresses (Drug Analysis '92).

                Equipement & Resources

• High technology analytical instrumentation:
  • Automated sample preparation with extraction cartridges (ASPEC system);
  • Automated sequential trace enrichment of dialysates (ASTED system);
  • High performance liquid chromatography (HPLC) : 7 instruments with various detectors (UV-visible variable-wavelength and diode-array, fluorometric and electrochemical detectors) and one micro-LC instrument;
  • Gaz chromatography coupled to flame ionisation (FID) and mass spectrometric detection (GC-MS);
  • Capillary electrophoresis (CZE, MEKC) : 3 instruments;
  • Atomic spectroscopy (AAS, AES);
  • UV-visible spectrophotometry;
  • Karl Fischer equipment, polarimeter, melting point instrument, automated titrators and laminar air flow equipments.
• Quality assurance unit.
• Compliance with GLP rules.

                Publications

More than 200 articles in international literature, for example:

• J. CROMMEN et al., "Indirect detection in liquid chromatography - II. Response models for reversed-phase non-ionic systems", Chromatographia, 25, 397-403 (1988).
• PH. HUBERT et al., "Knowledge-based system for the automated solid-phase extraction of basic drugs from plasma coupled with their liquid chromatographic determination : application to the biodetermination of b-receptor blocking agents", J. Chromatogr. A, 665, 87-99 (1994).
• I. BECHET et al., "Chiral separation of basic drugs by capillary zone electrophoresis with cyclodextrin additives", Electrophoresis, 15, 818-823 (1994).
• L. FOTSING et al., "Determination of six water-soluble vitamins in a pharmaceutical formulation by capillary electrophoresis", J. Pharm. Biomed. Anal., 15, 1113-1123 (1997).
• A. CECCATO et al., "Simultaneous determination of methylphenobarbital enantiomers and phenobarbital in human plasma by on-line coupling of an achiral precolumn to chiral liquid chromatographic column", J. Chromatogr. A, 819, 143-153 (1998).
• M. FILLET et al., "Method development strategies for the enantioseparation of drugs by capillary electrophoresis using cyclodextrins as chiral additives", Electrophoresis, 19, 2834-2840 (1998).
• B. TOUSSAINT et al., "Determination of l-lysine n-acetylcysteinate, its mono- and dimeric related compounds by LC-MS", J. Chromatogr. A, 819, 161-170 (1998).
• PH. HUBERT et al., "The SFSTP Guide on the validation of chromatographic methods for drug bioanalysis : from the Washington Conference to the laboratory", Anal. Chim. Acta, 391, 135-148 (1999).
• P. CHIAP et al., "Validation of an automated method for the liquid chromatographic determination of atenolol in plasma : application of a new validation strategy", Anal. Chim.. Acta, 391, 227-238 (1999).

National and international collaboration with other universities (VUB, Pr Massart ; University of Monpellier, Pr Fabre ; University of Vienne, Pr Lindner ; University of Munster, Pr Blaschke ; University of Leiden, Pr Van der Greef) and numerous pharmaceutical companies.