Multinuclear NMR screening of pharmaceuticals using standardization by 2H integral of a deuterated solvent

Abstract

NMR standardization approach that uses the ²H integral of deuterated solvent for quantitative multinuclear analysis of pharmaceuticals is described. As a proof of principle, the existing NMR procedure for the analysis of heparin products according to US Pharmacopeia monograph is extended to the determination of Na⁺ and Cl^- content in this matrix. Quantification is performed based on the ratio of a ²³Na (³⁵Cl) NMR integral and ²H NMR signal of deuterated solvent, D₂O, acquired using the specific spectrometer hardware. As an alternative, the possibility of ¹³³Cs standardization using the addition of Cs₂CO₃ stock solution is shown. Validation characteristics (linearity, repeatability, sensitivity) are evaluated. A holistic NMR profiling of heparin products can now also be used for the quantitative determination of inorganic compounds in a single analytical run using a single sample. In general, the new standardization methodology provides an appealing alternative for the NMR screening of inorganic and organic components in pharmaceutical products.

Keywords: (23)Na NMR; (35)Cl NMR; Heparin; Inorganic ions; NMR spectroscopy; Standardization.