Determination of As, Cd, Hg and Pb in continuous use drugs and excipients by plasma-based techniques in compliance with the United States Pharmacopeia requirements

• Published in: Spectrochimica acta. Part B: Atomic spectroscopy 2017-12, Vol.138, p.14-17
• Main Authors: da Silva, Caroline Santos, Pinheiro, Fernanda Costa, do Amaral, Clarice Dias Britto, Nóbrega, Joaquim Araújo
• Format: Article
• Language: English
• Subjects: Analytical methods; Cadmium; Detection; Drug development; Drugs; Elemental impurities; Emission spectroscopy; Excipients; Experiments; Federal regulation; ICP-MS; ICP-OES; Impurities; Inductively coupled plasma mass spectrometry; Lead; Low concentrations; Mass spectrometry; Mass spectroscopy; Mercury; Mercury (metal); Microwave-assisted digestion; Pharmacology; Public health; Scientific imaging; Sensitivity analysis; USP 232/233
• ISSN: 0584-8547; 1873-3565
• DOI: 10.1016/j.sab.2017.10.004

Some inorganic impurities are toxic to human health even when present at low concentrations and therefore must be carefully monitored in products as continuous use drugs. This work aimed the development of a simple microwave-assisted digestion procedure for different types of drugs and excipients and the analytical determination of elemental impurities according to the new regulations of the United States Pharmacopeia (USP) 232 and 233 using inductively coupled plasma optical emission spectrometry (ICP-OES) or inductively coupled plasma mass spectrometry (ICP-MS). Eight drugs samples and two excipients of different brands were microwave-assisted digested with inverse aqua regia. Addition and recovery experiments were performed according to J values, once permissible daily exposure value is specific for each element and estimated according to the maximum daily dose of drug indicated by the label. Samples were spiked with values of 1.5J in order to check accuracies for As, Cd, Hg, and Pb. Recoveries obtained by ICP-OES ranged from 75 to 148% and for ICP-MS ranged from 74 to 120%. The limits of detection for ICP-OES ranged from 0.4 to 17mgkg−1 and for ICP-MS from 7.4 to 41.6μgkg−1. Both analytical methods were adequate in terms of accuracies and sensitivities. Considering the maximum daily dose, all drugs samples and excipients contained As, Cd, Hg and Pb below the maximum limits stipulated by USP since all of them presented contents below respective limits of detection. [Display omitted] •Development of a simple procedure based on microwave-assisted digestion•Fast determination of As, Cd, Hg and Pb by ICP-OES and ICP-MS•Analytical determination according to the new USP 232 and 233 regulations•Application to continuous use drugs