TY - UNPB

T1 - Determination of Trace Elements in Ibuprofen Drug Products Using Microwave-Assisted Acid Digestion and Inductively Coupled Plasma-Mass Spectrometry

AU - Holmfred, Else

AU - Alrijjal, Abdulla

AU - Chamberlain, C. Page

AU - Maher, Katharine

AU - Stürup, Stefan

PY - 2023/8/1

Y1 - 2023/8/1

N2 - 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 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 combined with spike recoveries was 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.

AB - 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 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 combined with spike recoveries was 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.

KW - Ibuprofen

KW - pharmaceuticals

KW - trace elemental impurities

KW - acid digestion

KW - ICP-MS

KW - Analytical chemistry

U2 - 10.2139/ssrn.4523633

DO - 10.2139/ssrn.4523633

M3 - Preprint

T3 - JPBA-D-23-01192

BT - Determination of Trace Elements in Ibuprofen Drug Products Using Microwave-Assisted Acid Digestion and Inductively Coupled Plasma-Mass Spectrometry

PB - Social Science Research Network (SSRN)

ER -