A Quantitative Approach for the Determination of Elemental Impurities in Zinc Orotate Dihydrate Drug Substance by ICP-MS Method

Abstract

These days elemental impurities are commonly present in active pharmaceutical ingredients, raw materials, during the synthesis of compounds, drug excipients, finished products, equipment, containers and closures. Inductively coupled plasma mass spectrometry (ICP-MS) is one of the advanced techniques to analyze elemental impurities in drug substances. An ICP-MS method was developed and validated for testing 17 elements, namely, V, Co, Ni, As, Se, Ru, Rh, Pd, Ag, Cd, Os, Ir, Pt, Au, Hg, Tl, and Pb in zinc orotate dihydrate. The samples were analyzed after diluting with concentrated nitric acid and concentrated hydrochloric acid. Li, Y, Tl, Co and Ce were assigned tuning solutions to correct the baseline drift and matrix interference. The RF power was 1550 W, RF matching was 1.80 V, sample depth was 8.0 mm, nebulizer gas flow was 1.01 L/min, nebulizer pump flow was 0.10 rps, spray chamber temperature 2oC, He flow rate was 4.3 mL/min and the energy discrimination rate was 3.0 V. All 17 elements exhibited excellent linearity in their testing range, with a coefficient of determination ≥ 0.9996. The limits of detection of the 17 elements were within the range of 0.0004 to 0.00411 ppm. The intra- and inter-day precision (relative standard deviation) was <6.4%. The recoveries of the spiked standard for all elements were 88.5 to 108.2%. Among the 17 elements of the zinc orotate dihydrate, the measured results of all the 17 elements were within the specified range, and the results of all the elements were also satisfactory. The developed method was simple, rapid, and effective. This method can be a powerful tool and imperative technology for the quantification of compounds in drug substances and pharmaceutical industries.