Application of ICH Guidelines for the Assessment and Control of Elemental Impurities in Parecoxib Sodium by Graphite-Digestion and ICP-MS.

Abstract

Parecoxib sodium is a widely used parenteral cyclooxygenase 2 selective inhibitor to relieve acute postoperative pain following gynecologic laparotomy surgery. To ensure the quality of the drug, a detailed quality specification is indispensable. Nevertheless, it is unavoidable to introduce inorganic impurities during the drug preparation process and how to assess and control them matters. This study proposed an analytical procedure for the determination of elemental impurities (Cd, Pb, As, Hg, Co, V, Ni, Li, Sb, and Cu) in parecoxib sodium, where an easier and safer digestion protocol, graphite digestion, combined with an inductively coupled plasma-mass spectrometer (ICP-MS) was adopted when compared with microwave digestion. Moreover, the study also discussed whether should they be listed in specification to comply with ICH Q3D guidelines after test of process validation batches. Limit of quantitation (LOQ) of the above elemental impurities reached to 0.05, 0.125, 0.375, 0.075, 0.125, 0.25, 0.5, 6.25, 2.25 and 7.5 ppm, respectively, and recovery in accuracy item ranged from 90.2% to 129.9%, reflecting a sensitive and accurate method.