Crystallization of local anesthetic and adjuvant mixtures: a chemical analysis of the crystal precipitate composition

Introduction Local anesthetics are often mixed with other local anesthetics or adjuvants to enhance block duration and/or speed of onset. Recent studies described the appearance of significant microscopic crystallization in such mixtures. However, the impact of precipitation on solute concentration, as well as the chemical composition of these crystals, remained unclear. Methods Eight commonly used mixtures of local anesthetics and adjuvants, which have previously been found to cause significant crystallization, were assessed using a high-performance liquid chromatography-ultraviolet system to detect changes in solute concentration for 800 min (13.3 hours) after admixtures. In a second step, liquid chromatography-mass spectrometry was used to investigate the composition of precipitates formed in lidocaine+sodium bicarbonate and lidocaine+ropivacaine+sodium bicarbonate mixtures. Results The concentration of the assessed mixtures remained constant over time, indicating that precipitation did not significantly affect the concentration of local anesthetics in the mix. The precipitates appearing in lidocaine+sodium bicarbonate and lidocaine+ropivacaine+sodium bicarbonate mixtures are composed of pure local anesthetics. Discussion Our study reveals that no effect on local anesthetic concentration in the solution was apparent. Moreover, the precipitates forming in lidocaine/ropivacaine/sodium bicarbonate mixtures are composed of pure local anesthetics. Our findings might facilitate the design of future in vivo studies assessing the behavior of local anesthetics crystals.