Work

A novel microextraction method for further elemental impurity determination in oily pharmaceutical excipients by ICP-MS

Year: 2025

Type: article

Abstract: In this study, a reversed-phase dispersive liquid-liquid microextraction (RP-DLLME) method was proposed for the subsequent determination of elemental impurities of class 1 (As, Cd, Hg, and Pb) and class 2 A (Co, Ni, and V) in oily pharmaceutical excipients, as recommended by the International Council for Harmonisation (ICH) guideline Q3D. Analyte determination was carried out by inductively coupled plasma mass spectrometry (ICP-MS). Operational parameters were evaluated, including dispersant and extractant solvents, total volume and proportion of the extraction solution, sample mass, temperature, heating time, centrifugation, and stirring. Suitable results were obtained using a high sample mass (5 g), 2 mL of 50:50% (v/v) of n -propanol:HNO 3 (3 mol L -1 HNO 3 for all analytes and 6 mol L -1 HCl only for Hg), heating at 85 °C for 20 min, stirring for 1 min, and centrifugation for 10 min. Accuracy was assessed using certified reference materials (CRMs) of mineral oil, comparison with a reference method (microwave-assisted wet digestion), and analyte recovery experiments at three concentration levels, following ICH Q3D recommendations and the United States Pharmacopeia (USP) guidelines for injectable drugs. No statistical differences were observed in any of the accuracy assessments. The method achieved low quantification limits (LOQs) of 0.045, 0.006, 0.006, 0.009, 0.040, 0.020, and 0.102 µg g -1 for As, Cd, Co, Hg, Ni, Pb, and V, respectively, all of which were below the maximum levels allowed by the ICH guideline. The proposed method presented several advantages for routine analysis, including simplicity, high throughput, the use of diluted solutions, and minimal laboratory waste generation.

Source: Journal of Pharmaceutical and Biomedical Analysis Open

DOI: 10.1016/j.jpbao.2025.100063

Authors: Cristian Rafael Andriolli, Mariele Samuel Nascimento, Alessandra Schneider Henn, Eder Lisandro Moraes Flores, Erico Marlon Moraes Flores, Rochele Sogari Picoloto

Institutions: Universidade Federal de Santa Maria, Universidade Federal de Minas Gerais, Universidade Tecnológica Federal do Paraná

Language: English

Topic: Analytical chemistry methods development

Subfield: Analytical Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $1,540

Funders: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul