NMR Longitudinal Rotating Frame Relaxation Time (T) with a Weak Spin Locking Field as an Approach to Characterize Solid-State Active Pharmaceutical Ingredients: Proof of Concept

Anal Chem. 2024 May 28;96(21):8317-8324. doi: 10.1021/acs.analchem.3c04935. Epub 2024 May 13.

Abstract

Nuclear magnetic resonance (NMR) longitudinal rotating frame relaxation time (T), rarely used in low-field NMR, can be more effective than conventional T1 and T2 relaxation times to differentiate polymorphic forms of solid pharmaceuticals. This could be attributed to T sensibility to structural and molecular dynamics that can be enhanced by changing the strength of the oscillating magnetic field (B1) of spinlock pulses. Here, we compared the capacity of T1, T2, and T to differentiate inactive (A) and active (C) crystalline forms of the World Health Organization essential drug Mebendazole. The results showed that T1 and T2 values of both forms were statistically identical at 0.47 T. Conversely, T of both forms measured with weak spinlock B1 fields, ranging from 0.08 to 0.80 mT were statistically different in the same spectrometer. The T also has the limit of detection to detect the presence of at least 10% of inactive A form in the active C form. Therefore, T, measured with weak spinlock B1 fields can be an effective, streamlined, and complementary approach for characterizing not only solid active pharmaceutical ingredients but other solid-state materials as well.

MeSH terms

  • Bulk Drugs
  • Magnetic Fields
  • Magnetic Resonance Spectroscopy* / methods
  • Mebendazole / chemistry
  • Pharmaceutical Preparations / analysis
  • Pharmaceutical Preparations / chemistry
  • Proof of Concept Study

Substances

  • Mebendazole
  • Pharmaceutical Preparations
  • Bulk Drugs