Multiplatform Benchtop NMR Interlaboratory Study of Model Liquid Dosage Forms of Pharmaceutical Products.

Low-field NMR relaxometry uses water proton (1H2O) relaxation (wNMR) as a powerful and flexible tool to reveal deviations in critical quality attributes of liquid pharmaceuticals such as concentration or, in the case of proteins, aggregation. Measurements are fast and nondestructive, and many benchtop instruments can make measurements noninvasively, with an intact drug vial, prefilled syringe, or pen inserted directly into the probe. Because of the diversity of low-field instrument configurations and operating temperatures, the varying field strengths available, and the many possible protocols, pulse sequences, and parameters for conducting relaxation measurements, we sought to test the reproducibility of wNMR across platforms, and to identify the details of applying wNMR that impact reproducibility. To accomplish this, we piloted an interlaboratory study, in collaboration with benchtop NMR instrument vendors, using model liquid dosage forms of pharmaceutical products in sealed vials. This study demonstrates that when suitable measurement protocols are employed, wNMR measurements from all instruments can track the concentrations of diverse samples with high linearity. Furthermore, wNMR measurements were capable of detecting intentionally included outlier samples. This study revealed various operating procedures and variables that contributed more to measurement variance than any hardware- or instrument-specific differences. Based on these results, we offer initial considerations for harmonizing measurement protocols to enable reliable wNMR analysis of pharmaceuticals.