Study and determination of elemental impurities by ICP-MS in active pharmaceutical ingredients using single reaction chamber digestion in compliance with USP requirements

Abstract

In this work a method for active pharmaceutical ingredients (APIs) digestion using the single reaction chamber (SRC-UltraWave™) system was proposed following the new recommendations of United States Pharmacopeia (USP). Levodope (LEVO), primaquine diphosphate (PRIM), propranolol hydrochloride (PROP) and sulfamethoxazole (SULF) were used to evaluate the digestion efficiency of the proposed method. A comparison of digestion efficiency was performed by measuring the carbon content and residual acidity in digests obtained using SRC and in digests obtained using conventional microwave-assisted digestion system (Multiwave(TM)). Three digestion solutions (concentrated HNO3, aqua regia or inverse aqua regia) were evaluated for digestion of APIs. The determination of Cd, Ir, Mn, Mo, Ni, Os, Pb, Pd, Pt, Rh, Ru was performed using inductively coupled plasma mass spectrometry (ICP-MS) in standard mode. Dynamic reaction cell (DRC) mode was used for the determination of (51)V, (52)Cr, (53)Cr, (63)Cu and (65)Cu in order to solve polyatomic ion interferences. Arsenic and Hg were determined using chemical vapor generation coupled to ICP-MS (FI-CVG-ICP-MS). Masses of 500mg of APIs were efficiently digested in a SRC-UltraWave™ system using only HNO3 and allowing a carbon content lower than 250mg L(-1) in final digests. Inverse aqua regia was suitable for digestion of sample masses up to 250mg allowing the determination of Ir, Pd, Pt, Rh and Ru. By using HNO3 or inverse aqua regia, suitable recoveries were obtained (between 91 and 109%) for all analytes (exception for Os). Limits of quantification were in agreement with USP requirements and they ranged from 0.001 to 0.015µg g(-1) for all elemental impurities (exception for Os). The proposed method was suitable for elemental impurities determination in APIs and it can be used in routine analysis for quality control in pharmaceutical industries.

Keywords: Active pharmaceutical ingredients (APIs); Elemental impurities; Microwave-assisted digestion; Polyatomic ion interferences.; Single reaction chamber (SRC).