Determination of trace elements in ibuprofen drug products using microwave-assisted acid digestion and inductively coupled plasma-mass spectrometry

Else Holmfred; Abdulla Alrijjal; C Page Chamberlain; Katharine Maher; Stefan Stürup

doi:10.1016/j.heliyon.2023.e23566

Determination of trace elements in ibuprofen drug products using microwave-assisted acid digestion and inductively coupled plasma-mass spectrometry

Heliyon. 2023 Dec 10;10(1):e23566. doi: 10.1016/j.heliyon.2023.e23566. eCollection 2024 Jan 15.

Authors

Else Holmfred^{1

2}, Abdulla Alrijjal³, C Page Chamberlain¹, Katharine Maher², Stefan Stürup³

Affiliations

¹ Department of Earth and Planetary Sciences, Stanford University, Stanford, CA, USA.
² Department of Earth System Sciences, Stanford University, Stanford, CA, USA.
³ Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.

Abstract

Trace elements are found in most drugs as a result of the drug formulation and drug production methods. An inductively coupled plasma-mass spectrometry method for the determination of 24 trace elements (Mg, Ti, V, Cr, Mn, Cu, Fe, Co, Ni, Zn, As, Se, Mo, Ru, Rh, Pd, Ag, Cd, Sb, Ba, Ir, Pt, Au, and Pb) in solid ibuprofen tablets was established in relation to the ICH Q3D(R1) guideline, to evaluate the possibility of linking trace elemental profiles to drug formulation strategies, and to differentiate between drug products based on the trace elemental profiles. Ten European ibuprofen drug products were evaluated (n=3). The sample preparation was performed by microwave-assisted acid digestion using only 10 mg of homogenized sample and 900 μL of a mix of 65% HNO₃, 37% HCl, and 30% H₂O₂. Solid residuals primarily composed of insoluble SiO₂ excipients were removed by centrifugation. Only concentrations of Mg, Fe, Ti, Mn, Cr, and Ni were detected above the limits of detection and did not exceed the ICH Q3D(R1) guideline permitted daily exposure limits. The trace elemental profiles were evaluated through principal component analysis. Three principal components describing 96% of the variance were useful in grouping the ibuprofen drug products, and the detected trace elemental remnants could be related to drug formulation and drug production strategies. An in-house quality control material was used in lack of certified reference materials and was in combination with spike recoveries used for method validation. Good spike recoveries (94-119%) were obtained for all measured trace elements except Mg. Mg showed acceptable spike recoveries (75-155%) for mid and high-spike concentrations, but poor recoveries (30-223%) were detected with low spike concentrations in spike matrices containing high amounts of Mg. Overall, the method is suggested applicable for solid drugs containing insoluble SiO₂ excipients and drugs comparable to ibuprofen.

Keywords: Acid digestion; Analytical chemistry; ICP-MS; Ibuprofen; Pharmaceuticals; Trace elemental impurities.