Determination of Palladium as an Elemental Impurity in Ropivacaine Hydrochloride Monohydrate by Atomic Absorption Spectrometer

According to an International Conference on Harmonization (ICH), a catalyst used during the synthesis process of drugs may be present in trace levels in the final product. These elemental impurities must thus be quantified in drugs. Ropivacaine hydrochloride monohydrate is a prolonged acting amide local anesthetic. Synthesis of ropivacaine requires hydrodehalogenation of 2-butyl-4-chloro-5-formylimidazole to 2-substituted 5-formylimidazole in the presence of palladium as the catalyst. The amount of palladium used ranges from 5% to 15% based on the weight of 2-butyl-4-chloro-5-formylimidazole. There are high chances that palladium as an elemental impurity may be present in large amounts in the final product, causing toxicity to the body. A simple, efficient, accurate, specific, cost-effective, validated method was developed to estimate palladium content as an elemental impurity in ropivacaine hydrochloride monohydrate using atomic absorption spectroscopy (AAS) with a 0.2-nm slit width and a palladium hollow cathode lamp. Acetylene and air mixture were used for the flame, with a wavelength of 247.60 nm. The system performance was evaluated by performing the system suitability parameters. The limit of detection and limit of quantification (LOQ) were found to be 0.03 mg/mL and 0.10 mg/mL respectively. Palladium response was measured both in a blank matrix and in a sample matrix. As there is a lack of interference from both matrices, the approach was determined to be specific. The method was found to be linear from 0.10 mg/L to 1.00 mg/L. Recoveries of accuracy studies were performed at three spiking levels at LOQ 50%, 100%, and 150%, and the results were found to be 101.45, 100.65, 100.40, and 100.21[PF1]% respectively. The method precision and intermediate precision parameter demonstrate the degree to which readings agree with one another, on different days by different analysts. It concludes that this developed and validated atomic absorption spectroscopy method for determining palladium in ropivacaine hydrochloride monohydrate substance was within the permitted limit.