Greening microwave-assisted digestion method using hydrogen peroxide for determination of elemental impurities by ICP-OES in antihypertensive active pharmaceutical ingredients

Abstract

Microwave-assisted wet digestion (MAWD) using only H₂O₂ was proposed for oxidizing active pharmaceutical ingredients (APIs) for hypertension treatment and subsequent determination by inductively coupled plasma optical emission spectrometry (ICP-OES). Diltiazem hydrochloride (DIL) presented the most refractory characteristic for oxidation using MAWD-H₂O₂. This proposed MAWD-H₂O₂ method was validated for specificity, accuracy, and precision according to United States Pharmacopeia (USP) Chapter 233 guidelines. Regarding specificity, the most sensitive emission lines were utilized to analyze all elemental impurities in the digests, and no significant spectral interferences were observed. Sample masses of 500 mg for all APIs and a digestion temperature of 250 °C provided digests with residual carbon (RC) below 2400 mg L^-1 of C. Additionally, the residual acidity of the MAWD-H₂O₂ digests was lower than the acidity presented by the HNO₃ digests. The highest and lowest residual carbon content (RCC) for digests were observed for DIL and captopril (CAP), respectively, using MAWD-H₂O₂. When comparing the RCC for MAWD-H₂O₂ and MAWD-HNO₃ digests for APIs containing aromatic rings, it was evident that H₂O₂ offered equivalent conditions for digesting these compounds. Accuracy tests showed recovery values of 91-110% for all elemental impurities, as recommended by USP chapter 233. Validation experiments for precision presented relative standard deviation (RSD) values below 6.4% and 10% under repeatability and intermediate precision conditions, respectively. The limits of quantification (LOQs) provided by MAWD-H₂O₂ are at most half of those recommended by of USP and International Council for Harmonisation of Technical Requirements (ICH). In conclusion, MAWD-H₂O₂ can be considered an alternative method for API digestion, aligning with green analytical chemistry principles, as it does not employ toxic reagents, minimizes waste, and the main products of H₂O₂ oxidation are water and oxygen. Considering the analytical Eco-Scale, the MAWD-H₂O₂ method scored 81, classifying it as an excellent green analysis.

Keywords: Active pharmaceutical ingredients; Elemental impurities; Hydrogen peroxide; Microwave-assisted wet digestion.