Spectrophotometric methods. UV spectrophotometry is occasionally used to determine purity. Since it depends upon the presence of a characteristic chromophore, it can detect impurities that contribute excessively to the absorbance value and may indicate the presence of impurities that have a negligible or distinctive absorbance.

However, the utility of the method is limited by the small number of absorption maxima in the UV range, the large numbers of compounds containing similar characteristic chromophores, and the need for an external chemical reference substance.

IR spectrophotometry may be used to identify and determine the proportions of geometric isomers. NMR spectroscopy, a powerful spectroscopic identification tool, is also occasionally useful in the determination of purity.

Titrimetric methods. Titrimetric methods provide a valuable means of confirming the identity and purity of a proposed chemical reference substance and are useful in confirming purity values obtained by other methods.

Optical rotation methods. Many chemical reference substances are optically active and the relative proportion of optical isomers can sometimes be determined by an optical rotation method, but generally such methods lack sensitivity. However, the quantitative use of these techniques is well established and can yield results of high precision, depending on the solvent and the wavelength chosen for measurement. Chiral chromatography and NMR are becoming increasingly important.

Determination of water and organic volatiles. It is essential that an accurate assessment of the moisture content and the content of volatile contaminants be made. These total values may often be obtained by drying under defined conditions that are appropriate to the proposed substance. Sometimes this may not be possible or may yield misleading results. In such cases, thermogravimetric analysis may be used to determine the water and volatile content. Alternatively, the water content may be determined by Karl Fischer titration and the content of volatile solvents by GC. Without an accurate assessment of these values at the time that other determinations are being made, judgements of the acceptability of the proposed chemical reference substance will be invalid.