An update on the current status and prospects of nitrosation pathways and possible root causes of nitrosamine formation in various pharmaceuticals.
AI, acceptable intake
APIs, active pharmaceutical ingredients
ARBs, angiotensin II receptor blockers
AZBC, 4′-(azidomethyl)-[1.1′-biphenyl]-2-carbonitile
AZBT, 5-(4′-(azidomethyl)-[1,1′-biphenyl]-2-yl)-1H-tetrazole
AZTT, 5-(4′-((5-(azidomethyl)-2-butyl-4-chloro-1H-imidazol-1-yl) methyl)-[1,1′-biphenyl]-2-yl)-1H-tetrazole
CDER, center for drug evaluation and research
CPNP, 1-cyclopentyl-4-nitrosopiperazine
Control limits
DBA, N,N-dibutylamine
DEA, N,N-diethylamine
DIPEA, N,N-diisopropylethylamine
DMA, dimethylamine
DMF, N,N-dimethyl formamide
DPA, N,N-dipropylamine
EMA, European Medicines Agency
EPA, Environmental Protection Agency
FDA, Food and Drug Administration
HSA, Health Sciences Authority
IARC, International Agency for Research on Cancer
ICH, International Council for Harmonisation
LD50, median lethal dose
MBA, N-methylamino-N-butyric acid
MDD, maximum daily dose
MNP, 1-methyl-4-nitrosopiperazine
NAP, nitrosation assay procedure
NDBA, N-nitrosodibutylamine
NDEA, N-nitrosodiethylamine
NDIPA, N-nitrosodiisopropylamine
NDMA, N-nitrosodimethylamine
NDSRIs, Nitrosamine drug substance-related impurities
NEIPA, N-nitroso ethylisopropylamine
NMBA, N-nitroso-N-methyl-4-aminobutyric acid
NMP, N-methyl pyrrolidinone
NOCs, N-nitroso compounds
Nitrosamines
Nitrosation
PPRs, proportionate reporting ratios
Ranitidine
SARs, structure–activity relationships
Sartans
TD50, median toxic dose
TEA, triethylamine
TMA, trimethylamine
TTC, threshold of toxicological concern
USFDA, United States Food Drug and Administration
USP, United States Pharmacopoeia
WHO, World Health Organization
Journal
Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society
ISSN: 1319-0164
Titre abrégé: Saudi Pharm J
Pays: Saudi Arabia
ID NLM: 9705695
Informations de publication
Date de publication:
Feb 2023
Feb 2023
Historique:
received:
24
05
2022
accepted:
18
12
2022
entrez:
21
3
2023
pubmed:
22
3
2023
medline:
22
3
2023
Statut:
ppublish
Résumé
Over the last two years, global regulatory authorities have raised safety concerns on nitrosamine contamination in several drug classes, including angiotensin II receptor antagonists, histamine-2 receptor antagonists, antimicrobial agents, and antidiabetic drugs. To avoid carcinogenic and mutagenic effects in patients relying on these medications, authorities have established specific guidelines in risk assessment scenarios and proposed control limits for nitrosamine impurities in pharmaceuticals. In this review, nitrosation pathways and possible root causes of nitrosamine formation in pharmaceuticals are discussed. The control limits of nitrosamine impurities in pharmaceuticals proposed by national regulatory authorities are presented. Additionally, a practical and science-based strategy for implementing the well-established control limits is notably reviewed in terms of an alternative approach for drug product
Identifiants
pubmed: 36942272
doi: 10.1016/j.jsps.2022.12.010
pii: S1319-0164(22)00309-7
pmc: PMC10023554
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
295-311Informations de copyright
© 2022 The Author(s).
Déclaration de conflit d'intérêts
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.
Références
Comput Toxicol. 2021 Nov;20:
pubmed: 34901581
Regul Toxicol Pharmacol. 2019 Apr;103:325-329
pubmed: 30629969
Carcinogenesis. 1983 Oct;4(10):1281-5
pubmed: 6311451
Chem Pharm Bull (Tokyo). 2020 Oct 1;68(10):1008-1012
pubmed: 32779580
N Engl J Med. 2019 Apr 25;380(17):1589-1591
pubmed: 30865819
Regul Toxicol Pharmacol. 2021 Jul;123:104926
pubmed: 33862169
Chem Res Toxicol. 2022 Mar 21;35(3):475-489
pubmed: 35212515
RSC Adv. 2019 May 1;9(24):13403-13413
pubmed: 35519592
J Vis Exp. 2017 Sep 25;(127):
pubmed: 28994777
J Pharm Biomed Anal. 2021 Oct 25;205:114300
pubmed: 34365191
Cancers (Basel). 2020 Dec 23;13(1):
pubmed: 33374592
J Am Chem Soc. 2002 Oct 16;124(41):12210-6
pubmed: 12371861
Int J Environ Res Public Health. 2022 Sep 30;19(19):
pubmed: 36231768
J Environ Sci (China). 2017 Aug;58:116-126
pubmed: 28774600
Arh Hig Rada Toksikol. 2021 Mar 30;72(1):1-5
pubmed: 33787187
Toxicol Appl Pharmacol. 2008 Sep 1;231(2):197-207
pubmed: 18533217
J Food Drug Anal. 2019 Oct;27(4):915-925
pubmed: 31590763
Front Med (Lausanne). 2021 Nov 19;8:782536
pubmed: 34869504
Science. 1973 Sep 28;181(4106):1245-7
pubmed: 4726444
J Pharm Sci. 2021 Sep;110(9):3118-3128
pubmed: 33989680
J Med Chem. 1982 Feb;25(2):178-82
pubmed: 6460102
J Med Chem. 1991 Aug;34(8):2525-47
pubmed: 1875348
J Food Drug Anal. 2021 Mar 15;29(1):39-45
pubmed: 35696227
J Med Chem. 2021 Mar 25;64(6):2923-2936
pubmed: 33706513
Int J Mol Sci. 2022 Apr 20;23(9):
pubmed: 35562949
Expert Opin Drug Saf. 2021 Jul;20(7):855-862
pubmed: 33849366
Healthcare (Basel). 2021 Aug 20;9(8):
pubmed: 34442208
Water Res. 2011 Jan;45(2):944-52
pubmed: 20950838
Crit Rev Anal Chem. 2022;52(1):53-71
pubmed: 32691615
Chem Pharm Bull (Tokyo). 2021;69(9):872-876
pubmed: 34470951
J Org Chem. 2021 Feb 5;86(3):2037-2057
pubmed: 33474939
Arch Pharm (Weinheim). 2022 Apr;355(4):e2100435
pubmed: 35088435
Cancer Res. 1991 Dec 1;51(23 Pt 2):6452-69
pubmed: 1933907
J Am Chem Soc. 2001 Oct 24;123(42):10164-72
pubmed: 11603965
Arch Pharm (Weinheim). 1995 Feb;328(2):137-42
pubmed: 7726739
Water Res. 2015 Dec 15;87:403-11
pubmed: 26469132
Carcinogenesis. 2016 Jun;37(6):625-634
pubmed: 26992900
Regul Toxicol Pharmacol. 2020 Oct;116:104749
pubmed: 32777431
J Org Chem. 2017 Jun 2;82(11):5769-5781
pubmed: 28472882
Environ Sci Technol. 2012 Oct 16;46(20):11095-103
pubmed: 22967139