Measurement of Elemental Impurities in a Higher Daily Dose Drug Product by USP <232>/<233> Using Ultrasonic Nebulization with ICP-AES Detection

Abstract: On January 1, 2018 the U.S. Pharmacopeia (USP) enacted new criteria for element impurities in finished drug products. These criteria, detailed in USP/, recommend analysis of drug products for element impurities by either ICP-AES or ICP-MS. Laboratories must measure impurities based on a J value for each drug product; drug products may be oral, parenteral (ex. intravenous, injection), or inhalation types. The J value of the drug is calculated based on an established permissible daily exposure (PDE), maximum daily dose of the drug (MDD), and the dilution factor used in the sample preparation method. As a result of the J value calculation, drugs with a larger MDD require lower element impurity detection limits. An ultrasonic nebulizer (USN) is an accessory for ICP-AES that enables higher sample transport efficiency (versus a standard pneumatic nebulizer) to the ICP-AES plasma. This benefit can be helpful for detection of more difficult elements such as As, Cd, Pb, Sb, and Tl. This work describes the use of the USN for ICP-AES detection of element impurities in aspirin, a drug with a higher daily dose than a low dose drug (ex. 1 tablet per day) such as an allergy or sleep aid medicine.