A Survey of Material Science and Physical Characterization Techniques and Equipment for Small Molecules - Part II

Material science and physical characterization are crucial to ensure drug products’ or drug substances’ identities with measurements and analysis.¹ There are many types of techniques and equipment to do this, each with its own features and qualities. In this blog, the second part of a series, we will review the advantages of various techniques and equipment.

We begin our second overview with Thermogravimetric Analysis (TGA), a quantitative analytical technique. It is a very old technique, with the first gravimetric test recorded in 27 B.C. by Vitruvius, who measured the change in mass of limestone as it calcined to lime.² It can be used for many applications, including food, glass, polymer science, and materials.³

While applying TGA, the mass of a sample is monitored at a furnace temperature as high as 1600°C under a stable or changing gas flow. Sample size can range from around 1mg to several g.² For active pharmaceutical ingredient (API) analysis, it is useful for detecting residual volatiles and inorganics.

Fourier-Transform Infrared Spectroscopy (FTIR), within the API space, identifies materials with “the quantitative analysis of complex mixtures, as well as for the investigation of surface and interfacial phenomena.”⁴ Since no two unique molecular structures produce the same (infrared) IR spectrum, it is a useful technique for rapid, economical, easy, and nondestructive identification.

A Nature Review Methods Primers article defines mass spectrometric analysis as “based on the separation of ions by their mass to charge ratio (m/z).”⁵ There are two major types of Mass Spectroscopy (MS), Gas and Liquid Chromatography (GC and LC). Gas Chromatography-Mass Spectroscopy (GCMS) is one of the most important and prevalent analytical tools available to chemists. It was invented in 1952 by A.T. James and A.J.P. Martin as an outgrowth of research dating back to the 1940s. It is useful for identification. Some other analyses that GC can do include separating compounds in mixtures based on the polarity of the compounds, testing for purity – or impurities, e.g., and detecting residual solvents. Additionally, with a technique known as preparative chromatography, GC can be used to prepare pure compounds from a mixture. In pharmaceutical analysis, there are additional applications:

Analysis of various functional groups.
Determining purity of pharmaceutical compounds.
Analysis of drugs that are commonly abused.
Determination in pharmaceutical R & D the identity of natural products containing complex, similar compound mixtures.
Use in metabolomics studies.

Liquid Chromatography Mass Spectroscopy (LCMS) is now a fairly common technique that combines chromatography with the sensitive and highly specific nature of MS as compared to other chromatographic techniques. In LC, “molecules are separated based on differential equilibrium between a mobile phase and a stationary phase.”⁵ The reasons for utilizing LCMS are similar to those for GCMS: its high specificity and ability to handle complex mixtures.⁶ It is seeing routine use in the clinical lab as well.

Finally, Nuclear Magnetic Resonance (NMR) spectroscopy is a well-established, common, and useful tool for chemists, which can be applied to all states of matter.⁷ It was first demonstrated by Felix Bloch et al..⁸ and Edward Purcell et al.⁹ working independently immediately after World War II. Subsequently, they both were awarded the Nobel Prize in Physics in 1952 for their work.¹⁰ There have been continued updates to the technique, resulting in two later Noble Prizes (1991 and 2002). NMR “is a physical phenomenon in which nuclei in a magnetic field absorb and re-emit electromagnetic radiation.”¹¹ Although it is commonly known as an imaging tool for healthcare, it is available for drug identification, determining the level of impurities, evaluating residual solvents, and establishing assays.

SK pharmteco Analytical Services has all of the equipment and techniques elucidated in this series. We can support all analytical requirements for pharmaceutical intermediates, Active Pharmaceutical Ingredients (APIs), and formulated drug products. Please contact us with any specific questions or to receive a quote for your material science and physical characterization.

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