Heteronuclear Two‐Dimensional NMR for Quantification of Candesartan Cilexetil

One-dimensional quantitative NMR (qNMR) has been predominantly applied to accurately quantify pharmaceutical compounds. However, its application to complex molecules is limited due to several challenges, such as signal response overlap and spectral complexity in ¹H qNMR, prolonged acquisition times for ¹³C, and the potential absence of relevant nuclei for ¹⁹F or ³¹P NMR. In ¹H qNMR, complex overlapping NMR peaks in a spectrum hinder quantification by restricting the selection of integration ranges. Specifically, selecting the correct signal response for integration is a major limitation. For example, while developing ¹H qNMR methods, signal responses of the target analyte and impurities could occur in the same chemical shift region, leading to measurement errors. Nowadays, two-dimensional (2D) qNMR is emerging as a viable quantitative technique to overcome such limitations. In this work, the application of the 2D NMR method (¹H-¹³C heteronuclear single-quantum coherence spectroscopy [HSQC]) was established to perform quantitative analysis for candesartan cilexetil, thus allowing a more precise quantitation method for a spectrum with complex signal patterns. Quantifying candesartan cilexetil using a 2D ¹H-¹³C HSQC experiment gives a good correlation between the measured and the actual sample weight. The study confirmed that the purity and sample weight can be measured accurately. The present study concludes that advanced NMR approaches can be utilized for the quantification of complex molecules. These advanced 2D qNMR approaches can be extended to other complex molecules and adopted using low-field benchtop instruments.