Temperature resolved second harmonic generation to probe the structural purity of m-hydroxybenzoic acid

We report the use of second harmonic generation (SHG) and temperature resolved second harmonic generation (TR-SHG) for in situ probing and monitoring the structural purification of m-hydroxybenzoic acid (MHBA). Pure and mixtures of the two polymorphic forms of MHBA (metastable Pna2₁ and stable P2₁/c) and commercial MHBA were analysed by: DSC, XRPD and SHG. Results obtained with these three techniques are compared and demonstrate for that particular component, the high sensitivity and accuracy of SHG in assessing the polymorphic purity of MHBA. The SHG detection threshold for the metastable polymorph is circa 2 ppm and is several orders of magnitude better than the sensitivity of XRPD (1 wt%) and DSC (only 17 wt%). The proportion of the metastable phase in the commercial MHBA was evaluated to 1 wt% by SHG. Results of TR-SHG measurements performed on commercial MHBA at 5 K min^?1 heating rate show that TR-SHG is a good technique for an in situ monitoring of the structural purity. The present study clearly demonstrates that SHG and TR-SHG are relevant and accurate techniques for probing the structural purity and for the monitoring of solid–solid phase transitions provided one of the two varieties crystallizes in a non-centrosymmetric space group.