On Problems with Liquid Chromatographic Quantification of Chiral 2-arylpropionic Acids by Use of Uv-absorption-based Detection

In previous publications we reported abundant empirical evidence of the spontaneous oscillatory transenantiomerization of optically pure enantiomeric 2-arylpropionic acids (2-APAs), resulting in a racemic mixture of the pairs of enantiomers. Our experiments were performed with 2phenylpropionic acid, ibuprofen, and naproxen. The last two compounds are non-steroidal anti-inflammatory drugs (NSAIDs) very popular throughout the world and sold in most countries over the counter. Before publication of our results pharmaceutical scientists were firmly convinced that the curative power of the S-(+) enantiomers of the 2-APAs was much greater than that of the R-(−) enantiomers. In this paper we will show that – because of the spontaneous oscillatory transenantiomerization of the 2-APAs – not only is the conformational instability of these compounds when dissolved in very simple low-molecular mass solvents (e.g. water, ethanol, etc.) well proved, but also that they cannot be precisely quantified by use of liquid chromatographic detectors based on absorption of UV light. Quantification by means of HPLC–UV, HPLC–DAD, and TLC–densitometry is burdened by substantially more experimental error than for compounds that do not spontaneously racemize by keto–enol tautomerism.