Acid borne oxidative impurities of Naloxone hydrochloride injection: Enrichment, isolation and characterization

Praveen Basappa Venugopala Rao Dama M. S. Uma Shankar   

Open Access   

Published:  Jun 16, 2022

Abstract

Herein, we report the identification, isolation, and characterization of two unidentified, unspecified degradant impurities of Naloxone hydrochloride injection USP , 2 mg/2 ml solution. These impurities are predominantly observed during the sixth month accelerated stability condition at 40°C/75%RH and found to be increased to the levels of 0.10% and 0.17%, respectively, by using high-performance liquid chromatography (HPLC) with UV detection. Enrichment of these impurities was successfully achieved in acidic stress conditions and the formation of these impurities, as indicated by HPLC, were found to be like 2.14% and 4.64%, respectively. Further the impurities were detected, identified, isolated, and characterized by using various analytical techniques such as gradient reverse-phase HPLC, liquid chromatography-tandem mass spectrometry, reverse-phase preparative liquid chromatography, nuclear magnetic resonance (NMR) and elemental analysis. The unknown impurities structures were proposed as (4R,4aS,7aR,12bS)-3- allyl-4a,9-dihydroxy-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e] isoquinolin-7(7aH)-one (degradation impurity-I) and (4bS, 5R, 8aS, 9R)-11-allyl-3,4,5,8a-tetrahydroxy-8,8a,9,10-tetrahydro-5H-9,4b-(epiminoethano) phenanthrene-6, 7-dione (degradation impurity-II). Structural elucidation of these impurities was performed by onedimensional and two-dimensional spectral data (1H NMR, 13C NMR, DEPT and 1H-1HgDQFCOSY, gHMBC, gHSQC, 1H-1HgROESY, MS, MS/MS, and elemental composition). The most plausible mechanism for the formation of impurities I and II were discussed in details.


Keyword:     Naloxone Hydrochloride Stability Degradants preparative HPLC NMR Mechanistic pathway


Citation:

Basappa P, Dama VR, Uma Shankar MS. Acid borne oxidative impurities of naloxone hydrochloride injection: Enrichment, isolation and characterization. J Appl Pharm Sci, 2022. Online First.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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