Learning outcomes of the course unit
The course, articulated in theory lessons and individual practice training, is aimed to supply the necessary notions for the quali-qualitative analysis of organic compounds of pharmaceutical interest, based on European Pharmacopeia identification and limit tests and on reference separation and spectroscopic analytical techniques.
Course contents summary
Safety and first aid procedures in the chemical and pharmaceutical laboratory. Symbols, risk and safety phrases. Hazard chemicals handling procedures.
Drug organoleptic characters: physical state, color, odour. Solubility and its expressions. Solvent classification: polarity, hydrogen-bonding, Van der Waals forces; structure-solubility relationship; ionisation state-solubility relationship.
Liquid state: boiling point determination, Raoult's law, liquid-gas diagrams. Solid state: Amorphous and crystalline solids, melting point, impurities influences on melting point. Crystallisation as purification method: state diagrams, eutectic mixtures. Polymorphism: enantiotropic and monotropic polimorphs.
Sample treatment. Solvent extraction: liquid-solid, liquid-liquid extraction, partition coefficient, single and multiple extractions. Variables influencing extraction yields. Applications to pharmaceutical preparations.
Physical constants determination. Refractive index: measurement, qualitative and quantitative analysis of liquids. Specific rotation index: measurement; polarimeter. Optical purity of chiral drugs. Density. Relative and Absolute density measurement.
Qualitative and quantitative elemental analysis: combustion; Na fusion; elemental analysers. Functional groups analysis. Crystalline derivatives preparation. Analytical profiles of classes of drugs . Identification assays of sample compounds included in the European Pharmacopeia. Limit assays.
Molecular absorption spectroscopy. UV-Visible. Instrumentation. Qualitative analysis: UV spectrum-chemical structure correlations. Identification of reference simple and conjugated chromophores: pH and solvent effects. Quantitative analysis: Lambert-Beer law; calibration curve. Infrared Spectroscopy: instrumentation, applications to pharmaceutical analysis, identification of reference functional groups.
Mass Spectrometry: ion sources (EI, CI, FAB, ESI, APCI, MALDI); Mass Analyzers (magnetic sector, quadrupole, ToF, 3D and linear ion trap); Detectors; GC and LC coupling. Mass Spectrometry applications to pharmaceutical analysis.
Chromatography. Classification: gas and liquid chromatography. Instrumentation. Theory of chromatographic separations: retention time, efficiency, selectivity, capacity factor, resolution. Van Deemter equation. Chromatography separation techniques: liquid/liquid partition; liquid/solid absorption: TLC, HPLC, GC. HPLC detectors: UV-Vis, Photodiode Array; Fluorescence, Mass spectrometer).
Analytical method validation: linearity, accuracy, precision, repeatability and reproducibility, detection and quantitation limit. Calibration standards and quality controls. Reference guidelines.
V. CAVRINI, V. ANDRISANO: “Analisi Farmaceutica” – Esculapio, Bologna.
F.CHIMENTI: “Identificazione sistematica di composti organici” – Grasso, Bologna.
D.A. SKOOG, J.J.LEARY: “Chimica Analitica Strumentale” – EdiSES, Napoli.
F. SAVELLI, O. BRUNO: “Analisi Chimico Farmaceutica” – PICCIN, Padova
R.M. SILVERSTEIN, F.X. WEBSTER: "Identificazione spettroscopica di composti organici" - Ambrosiana Editrice, Milano.
A. VOGEL: “Chimica Organica Pratica” – Ambrosiana Editrice, Milano.
D. SICA, F. ZOLLO: "Chimica dei composti eterociclici farmacologicamente attivi" - PICCIN, Padova
EUROPEAN PHARMACOPEIA, 6th Edition.
The final examination will consist in a practical laboratory test, in a written exam and an oral exam.