Application of quantitative NMR in pharmaceutical analysis: Method qualification and potency determination for two new chemical entities in early-stage clinical studies.

Autor: Guo X; Analytical Development, Biogen Inc., Cambridge, MA 02142, United States. Electronic address: xun.guo@biogen.com., Miller W; Analytical Development, Biogen Inc., Cambridge, MA 02142, United States., Zangi M; Department of Chemistry, Saint Louis University, St. Louis, MO 63103, United States., McElderry JD; Analytical Development, Biogen Inc., Cambridge, MA 02142, United States.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2023 Sep 20; Vol. 234, pp. 115561. Date of Electronic Publication: 2023 Jul 05.
DOI: 10.1016/j.jpba.2023.115561
Abstrakt: Quantitative NMR (qNMR), being a well-established analytical tool featuring efficiency, simplicity as well as versatility, has been extensively employed in pharmaceutical and medicinal testing. In this study, two 1 H qNMR methods were developed to determine the %wt/wt potency of two new chemical entities (compound A and compound B) used in early clinical phase process chemistry and formulation development. The qNMR methods were demonstrated to be significantly more sustainable and efficient than the LC-based approach by substantially reducing the cost, hands-on-time, and materials consumed for testing. The qNMR methods were achieved on a 400 MHz NMR spectrometer equipped with 5 mm BBO S1 broad band room temperature probe. The methods with CDCl 3 (for compound A) and DMSO-d 6 (compound B) as solvent as well as commercially certified standards for quantitation were phase-appropriately qualified in terms of specificity, accuracy, repeatability/precision, linearity, and range. Both qNMR methods were demonstrated to be linear over the range of 0.8-1.2 mg/mL (80% to 120% of the nominal sample concentration of 1.0 mg/mL) with a correlation coefficient greater than 0.995. The methods were also demonstrated to be accurate with average recoveries ranging from 98.8% to 98.9% and 99.4-99.9% for compound A and compound B respectively as well as precise with %RSD of 0.46% and 0.33% for compound A and compound B respectively. The potency results of compound A and compound B determined by qNMR were compared with those determined by the conventional LC-based method and the qNMR results were demonstrated to be consistent with the LC-based method with absolute difference of 0.4% and 0.5% for compound A and B respectively.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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