1H NMR determination of 1,3-dicyclohexylurea, glutaric acid and triethylamine in medical four-arm poly(ethylene glycol)-N-hydroxysuccinimide-glutarate for better quality control

Abstract

Absorbable vascular sealing medical glue, which belongs to Class III medical devices, is a special new material for preventing the leakage of cerebrospinal fluid. Medical four-arm poly(ethylene glycol)-N-hydroxysuccinimide-glutarate (4-arm-PEG-SG) with a molecular weight of 20 000 is the main component of the absorbable medical glue. According to its quality standard, the quality control of residues 1,3-dicyclohexylurea (DCU), glutaric acid (GA) and triethylamine (TEA) is required. A rapid analytical method of quantitative ¹H nuclear magnetic resonance (¹H NMR) for the determination of residues DCU, GA and TEA in medical 4-arm-PEG-SG was established in the present study. The peaks at δ 1.56 (4H, m), δ 2.71 (4H, t, J = 6.7 Hz), and δ 2.42 (6H, q, J = 7.2 Hz) were selected for quantifying DCU, GA and TEA, respectively, with deuterated pyridine as the solvent and tetramethylsilane as the internal standard. The ¹H NMR assay was validated by several experimental parameters including specificity, linearity, accuracy, precision, robustness, limit of detection (LOD), limit of quantification (LOQ) and stability. The average recoveries obtained were in the range of 99.48–102.02% for all three residues. Compared with the HPLC and GC approaches, the proposed ¹H NMR method proved to be a powerful tool for quantification due to its unique advantages of simplicity, rapidity and high robustness, especially not requiring standard compounds for calibration curve preparation.