Stability-indicating HPLC assays for the determination of prilocaine and procaine drug combinations

Abstract

Stability-indicating, reversed phase high-performance liquid chromatographic (HPLC) methods have been developed for the determination of several procaine hydrochloride and prilocaine hydrochloride combinations. The separation and quantitation of epinephrine–prilocaine and epinephrine–procaine drug combinations were achieved on a phenyl column using a mobile phase of 80:20% v/v 25 mM phosphate buffer (pH 3.0) containing 50 mM heptanesulfonic acid sodium salt–acetonitrile at a flow rate of 1 ml min −1 and UV detection at 254 nm. The method showed linearity for the epinephrine and prilocaine hydrochloride mixture in the 0.25–2.5 and 8–200 μg ml −1 ranges, respectively. The intra- and inter-day relative standard deviations (RSDs) ranged from 0.26 to 2.05% and 0.04 to 0.61% for epinephrine and prilocaine hydrochloride, respectively. The epinephrine and procaine hydrochloride mixture yielded linear ranges of 0.25–2.0 and 5–100 μg ml −1 and intra- and inter-day RSDs ranged from 0.23 to 1.88% and 0.07 to 0.26% for epinephrine and procaine hydrochloride, respectively. The assays were shown to be suitable for measuring epinephrine–prilocaine and epinephrine–procaine combinations in their respective injection dosage forms. Stability-indicating HPLC assays were also developed for several other procaine drug combinations since their monographs are present in the USP 24; however, quantitation was not investigated since these combinations are not commercially available. A mobile phase consisting of 80:20% v/v 25 mM phosphate buffer (pH 3.0) containing 50 mM heptanesulfonic acid–acetonitrile was utilized for the levonordefrin–tetracaine–procaine drug combination, while a mobile phase consisting of 70:30% v/v 25 mM phosphate buffer (pH 3.0) containing 50 mM heptanesulfonic acid sodium salt–acetonitrile was utilized for the separation of levonordefrin–procaine–propoxycaine and norepinephrine–procaine–propoxycaine. All separations were achieved on a phenyl column at a flow rate of 1 ml min −1 and UV detection at 254 nm.