This work investigated the effect of DMSO‑d6 on the conformation of lidocaine and fenamates. Using lidocaine as a model compound, the study investigated the influence of DMSO‑d6 on the conformational preferences of fenamates, which have similar fragment structures to the molecule. The NOESY spectra of mefenamic, flufenamic and tolfenamic acid were compared in a mixture of scCO2 + DMSO‑d6 at the same state parameters as lidocaine (45 °C and 9 MPa). The two-position exchange model was used to calculate the proportions of fenamate conformer groups in scCO2 + DMSO‑d6. The addition of DMSO‑d6 did not significantly alter the conformation of mefenamic acid, and the ratio of conformers was determined to be 75.3 / 24.7, which is very close to the previously measured in pure scCO2. The results showed that the addition of DMSO‑d6 did not significantly alter the conformation of lidocaine and mefenamic acid. This suggests that adding 2 %, DMSO‑d6 can be used to evaluate the structure of poorly soluble drug compounds using the NOESY method in supercritical carbon dioxide. The findings of this study are encouraging.
