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Polarimetric detection in high-performance liquid chromatography (HPLC) might seem like a matter of course, especially in areas such as control of the optical purity of drugs or fingerprinting of herbal extracts. However, there are well founded reasons for the relatively low popularity of polarimetric detection in HPLC. Such reasons include, for example, the insufficient sensitivity of this type of detector when compared with photodiode array detection or evaporative light-scattering detection, or the economic factors. This paper, regarding an example of  R (–)-naproxen, discusses physical phenomena (i.e., gelation of organic solvents by small organic molecules, the effect of molecular rotors and oscillatory interconversion of chiral analytes) that might obstruct the quantification of profen drugs (more generally, of chiral low molecular carboxylic acids) with the use of HPLC with polarimetric detection. The discussed (or analogous) phenomena are even more general, which hamper the widespread application of polarimetric detection in HPLC.

Polarimetric Detection in HPLC of R (–)-Naproxen: Features and Intrinsic Weakness