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.
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.
Cai R, Crane E, Poneleit K, Paulozzi L. Emergency department visits involving nonmedical use of selected prescription drugs in the United States, 2004-2008. J Pain Palliat Care Pharmacother, 2010; 24(3):293-7. https://doi.org/10.3109/15360288.2010.503730
Desai S, Patel A, Gabhe SY. Isolation and characterization of impurities present in 8-chlorotheophylline. Indian J Pharm Sci, 2011; 73(1):79-84. https://doi.org/10.4103/0250-474X.89762
Drugs C on. Naloxone dosage and route of administration for infants and children: addendum to emergency drug doses for infants and children. Pediatrics, 1990; 86(3):484-5.
Gamal M. Analytical review: analytical techniques for hyoscine N butyl bromide. Analyst, 2020; 145. https://doi.org/10.1039/D0AN00076K
Goodrich PM. Naloxone hydrochloride: a review. AANA J, 1990; 58(1):14-6. Erratum in: AANA J 1990 Jun;58(3):216. PMID: 2180244.
Gupta K, Prasad A, Nagappa M, Wong J, Abrahamyan L, Chung FF. Risk factors for opioid-induced respiratory depression and failure to rescue: a review. Curr Opin Anaesthesiol, 2018; 31(1):110-9. https://doi.org/10.1097/ACO.0000000000000541
Huang C-q, Zuo H-y, Cao G-h, Chang L. Determination of related substances in naloxone hydrochloride injection by HPLC. J Shenyang Pharm Univ, 2016; (10):778-82.
ICH Guideline [Q1A(R2)]. Stability of new drug substances and drug products, 2003 .
Jarzyna D, Jungquist CR, Pasero C, Willens JS, Nisbet A, Oakes L, Dempsey SJ, Santangelo D, Polomano RC. American Society for Pain Management Nursing guidelines on monitoring for opioid-induced sedation and respiratory depression. Pain Manag Nurs, 2011; 12(3):118-145.e10. https://doi.org/10.1016/j.pmn.2011.06.008
Kehlet H, Holte K. Effect of postoperative analgesia on surgical outcome. Br J Anaesth, 2001; 87(1):62-72. https://doi.org/10.1093/bja/87.1.62
Koo CY, Eikermann M. Respiratory effects of opioids in perioperative medicine. Open Anesth J, 2011; 5(1):23-34. https://doi.org/10.2174/1874321801105010023
McPherson M. Strategies for the management of opioid-induced adverse effects. Adv Stud Pharm, 2008; 5(2):52-7.
Mycyk MB, Szyszko AL, Aks SE. Nebulized naloxone gently and effectively reverses methadone intoxication. J Emerg Med, 2003; 24(2):185-7. https://doi.org/10.1016/S0736-4679(02)00723-0
Panchagnula R, Sharma P, Khandavilli S, Varma MVS. RPHPLC method and its validation for the determination of naloxone from a novel transdermal formulation. Farmaco, 2004; 59(10):839-42. https://doi.org/10.1016/j.farmac.2004.06.002
Pattinson KTS. Opioids and the control of respiration. Br J Anaesth, 2008; 100(6):747-58. https://doi.org/10.1093/bja/aen094
Ramachandra B. Development of impurity profiling methods using modern analytical techniques. Crit Rev Anal Chem, 2017; 47(1):24- 36. https://doi.org/10.1080/10408347.2016.1169913
Ryan SA, Dunne RB. Pharmacokinetic properties of intranasal and injectable formulations of naloxone for community use: a systematic review. Pain Manag, 2018; 8(3):231-45. https://doi.org/10.2217/pmt-2017-0060
Tenenbein M. Continuous naloxone infusion for opiate poisoning in infancy. J Pediatr, 1984; 105(4):645-8. https://doi.org/10.1016/S0022-3476(84)80440-0
The British Pharmacopoeia 2007. The Stationary Office (TSO). Health Ministry, London, UK, 2006.
Venkatesan P, Valliappan K. Impurity profiling: theory and practice. J Pharm Sci Res, 2014; 6(7):254-9.
0 Absract views 0 PDF Downloads 0 Total views