Established acceptable intake for nitrosamines in medicines

Last updated

3 November 2025

Below is a list of established AI limits for some nitrosamine impurities. These apply for all routes of administration.

Nitrosamine structures are available in the print version below.

Established AI limits for some other N-nitroso-structures. N-Nitroso-structures that include N-nitrosoguanidines, N-nitroso-indoles and N-nitrosoureas impurities are listed separately.

Established acceptable intake for nitrosamines in medicines

Nitrosamine (CAS number, Abbreviation)	Source²	AI limit (ng/day)¹	CPCA Potency category	First published
N-Nitroso-acarbose / N-nitroso-4,6-dideoxy-4-[(1S,2S,3R,4S,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)cyclohexyl]-α-D-glucopyranosyl-(1→4)-α-D-glucopyranosyl-(1→4)-α-D-glucopyranosyl-(1→4)-D-glucopyranose	Acarbose	1500	5	31 July 2025
1-Methyl-4-nitrosopiperazine (16339-07-4, MeNP/MNP)	Sildenafil	400	3	3 November 2025
N-Nitroso-2,6-pipecoloxilidide / desbutyl bupivacaine nitroso impurity (3035512-94-5)	Bupivacaine	1500	4	3 November 2025
N-Nitroso-desmethyl-almotriptan	Almotriptan	18	1	3 November 2025
N-Nitroso-N-desethyl-amiodarone (678982-38-2)	Amiodarone	18	1	3 November 2025
N-Nitroso-berotralstat / (R)-1-(3-(aminomethyl)phenyl)-N-(5-((3-cyanophenyl)((cyclopropylmethyl) (nitroso)amino)methyl)-2-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide	Berotralstat	100	2	3 November 2025
(2S,4R)-N-(6-Bromopyridin-2-yl)-4-fluoro-1-nitrosopyrrolidine-2-carboxamide	Danicopan	1500	4	3 November 2025
N-Nitroso‐N-desmethyl‐diltiazem (3036581-85-5)	Diltiazem	100		3 November 2025
N-Nitroso-diethylamine (55-18-5, NDEA)	Entacapone	26.5		3 November 2025
N-Nitroso-doravirine dimer NDD	Doravirine	1500		3 November 2025
N-Nitroso-desmethyl-doxylamine / N-methyl-N-(2-(1-phenyl-1-(pyridin-2-yl)ethoxy)ethyl)nitrous amide	Doxylamine	100		3 November 2025
N-Nitroso hydroxychloroquine EP Impurity C / N-(4-((7-chloroquinolin-4-yl)amino)pentyl)-N-(2-hydroxyethyl)nitrous amide	Hydroxychloroquine	100	2	3 November 2025
N-Nitroso hydroxychloroquine EP Impurity D / N-(4-((7-chloroquinolin-4-yl)amino)pentyl)-N-ethylnitrous amide	Hydroxychloroquine	18	1	3 November 2025
N-Nitroso-hydroxyzine Impurity A / 1-((4-chlorophenyl)(phenyl)methyl)-4-nitrosopiperazine (2005-04-1)	Hydroxyzine	400	3	3 November 2025
N-Nitroso-mirdametinib / N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)(nitroso)amino)benzamide	Mirdametinib	78000		3 November 2025
N-Nitroso-morpholine (59-89-2, NMOR)	Molsidomine	127.0		3 November 2025
N-Nitroso-nadolol (134720-06-2)	Nadolol	1500	5	3 November 2025
N-Nitroso-methylaminoantipyrine / N-(1,5-dimethyl-3-oxo-2-phenylpyrazol-4-yl)-N-methylnitrous amide (73829-38-6, NMAA)	Metamizole	100	2	3 November 2025
N-Nitroso-methylethanolamine / N-(2-hydroxyethyl)-N-methylnitrous amide (26921-68-6, NMELA)	Nefopam	100	2	3 November 2025
N-Nitroso-nirogacestat / (S)-2-(((S)-6, 8-difluoro-1, 2, 3, 4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentyl(nitroso)amino)propan-2-yl)-1H-imidazol-4-yl)pentanamide	Nirogacestat	1500		3 November 2025
N-Nitroso-nirogacestat impurity 1 / (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)(nitroso)amino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentanamide	Nirogacestat	1500	5	3 November 2025
N-Nitroso-propafenone impurity B / (R,E)-N-(3-(2-cinnamoylphenoxy)-2-hydroxypropyl)-N-propylnitrous amide	Propafenone	100	2	3 November 2025
N-Nitroso-2,4-thiazole amine / N-((2-isopropylthiazol-4-yl)methyl)-N-methylnitrous amide (NNTA)	Cobicistat	18	1	3 November 2025
N-Nitroso venlafaxine EP Impurity D / N-(2-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl)-N-methylnitrous amide (2680662-11-5)	Venlafaxine	18	1	3 November 2025
N-Nitroso venlafaxine EP Impurity H / N-(2-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl)-N-(4-methoxyphenethyl)nitrous amide	Venlafaxine	100	2	3 November 2025
N-Nitroso-dimethylamine (62-75-9, NDMA)	Ranitidine	96.0		15 September 2019
N-Nitroso-dimethylamine (62-75-9, NDMA)	Nizatidine	96.0		15 September 2019
N-Nitroso-dimethylamine (62-75-9, NDMA)	Metformin	96.0		15 September 2019
N-Nitroso-benzathine / N-nitroso-N,N'-dibenzylethanediamine / N-benzyl-N-(2-(benzylamino)ethyl)nitrous amide (NNB)	Benzathine	18	1	31 July 2025
N-Nitroso-brinzolamide / (R)-4-(ethyl(nitroso)amino)-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide	Brinzolamide	100	2	31 July 2025
N-Nitroso-carvedilol / N-(3-((9H-carbazol-4-yl)oxy)-2-hydroxypropyl)-N-(2-(2-methoxyphenoxy)ethyl)nitrous amide (2248746-67-8)	Carvedilol	400	3	31 July 2025
N-Nitroso-frovatriptan / (6R)-6-[methyl(nitroso)amino]-6,7,8,9-tetrahydro-5H-carbazole-3-carboxamide	Frovatriptan	400	3	31 July 2025
N-Nitroso-norfloxacin / 1-ethyl-6-fluoro-7-(4-nitrosopiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (74011-53-3)	Norfloxacin	NMI		31 July 2025
N-Nitroso-despropyl-ropinirole / N-(2-(2-oxoindolin-4-yl)ethyl)-N-propylnitrous amide	Ropinirole	18	1	31 July 2025
N-Nitroso-safinamide / (2S)-2-[[4-[(3-fluorophenyl)methoxy]phenyl]methyl-nitrosoamino]propanamide (2657645-00-4)	Safinamide	400	3	31 July 2025
Default class specific threshold of toxicological concern TTC	-	18.0	Default limit	-
3-((Ethyl(nitroso)amino)methyl) benzenesulfonate (N-M8)	Dextromethorphan	18	1	29 July 2024
N-Nitroso-N-ethyl-benzylamine / N-benzyl-N-ethylnitrous amide (20689-96-7, NBEA)	-	18	1	29 July 2024
1-Methyl-4-nitrosopiperazine (16339-07-4, MeNP/MNP)	Rifampicin	400	3	20 July 2022 Updated 24 August 2023
1-Nitroso-pyrrolopiperidine	-	1500	4	24 August 2023
2-Nitroso-octahydrocyclopenta(c)pyrrole (54786-86-6)	Gliclazide	1700		24 August 2023
3-Amino-N-nitrosopiperidine (2819242-71-0)	Alogliptin	400	3	16 October 2023
4-(Methylnitrosoamino)-1-(3-pyridinyl)-1-butanone (64091-91-4, NNK)	-	100		5 January 2023
7-Nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo-[4,3-a]pyrazine (2892260-32-9, NTTP)	Sitagliptin	100	2	20 July 2022 Updated 29 July 2024
Nitroso impurity C” [N-(2,6-dimethylphenyl)-2-(4-nitrosopiperazin-1-yl)acetamide]	Ranolazine	400	3	24 August 2023
N-Nitroso-orphenadrine (NMOA)	Orphenadrine	18	1	24 August 2023
N-Nitroso-praziquanamine / [2-nitroso-2,3,6,7-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4(11bH)-one] (115822-46-3)	Arpraziquantel	1500	4	24 August 2023
N-Methyl-N-nitrosophenethylamine (13256-11-6, NMPEA)	-	8.0		5 January 2023
N-Nitroso-1,2,3,6-tetrahydropyridine (55556-92-8, NTHP)	-	37.0		20 July 2022
N-Nitroso derivative of rotigotine impurity B / N-(5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N-propylnitrous amide	Rotigotine	400	3	16 October 2023
N-Nitroso derivative of rotigotine impurity C / N-(5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N-(-2-(thiophen-2-yl)ethyl)nitrous amide	Rotigotine	1500	4	16 October 2023
N-Nitroso-2,6-pipecoloxilidide / desbutyl bupivacaine nitroso impurity (3035512-94-5)	Ropivacaine	1500	4	24 August 2023
N-Nitroso-acebutolol	Acebutolol	1500	4	15 October 2024
N-Nitroso-2-(7-methoxy-1-naphthyl)-N-[2-(7-methoxy-1-naphthyl)ethyl]ethylamine	Agomelatine	100	2	29 July 2024
N-Nitroso-ambroxol	Ambroxol	1500		24 August 2023 Updated 31 January 2024
N-Nitroso-apixaban impurity B / 5-[4-[3-carbamoyl-1-(4-methoxyphenyl)-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridin-6-yl]-N-nitrosoanilino]pentanoic acid	Apixaban	1500	4	24 April 2024
1-(2,3-Dichlorophenyl)-4-nitrosopiperazine (2221987-86-4)	Aripiprazole	400	3	31 January 2024
N-Nitroso-articaine / methyl 4-methyl-3-(2-(nitroso(propyl)amino)propanamido)thiophene-2-carboxylate	Articaine	1500	4	29 July 2024
N-Nitroso-aryl piperazine / N-nitroso-desalkylquetiapine (NDAQ)	Quetiapine	400	3	24 August 2023
N-Nitroso-atomoxetine	Atomoxetine	100		24 August 2023
N-Nitroso-atenolol (134720-04-0)	Atenolol	1500	4	24 August 2023
N-Nitroso-azacyclonol (1038-06-8)	Azacyclonol	400	3	31 January 2024
N-Nitroso-desmethyl-azelastine	Azelastine	100	2	31 January 2024
N-Nitroso-azithromycin	Azithromycin	NMI		24 August 2023
N-Nitroso-benazepril	Benazepril	1500	5	24 August 2023
3-(Dimethylamino)propyl 2-[benzyl(nitroso)amino]benzoate	Benzydamine	400	3	29 July 2024
N-Nitroso-betahistine (32635-81-7)	Betahistine	18	1	24 August 2023
N-Nitroso-betaxolol	Betaxolol	1500	4	31 January 2024
N-Nitroso-bilastine impurity 2 / 1-(2-ethoxyethyl)-2-(1-nitrosopiperidin-4-yl)-1H-benzo[d]imidazole	Bilastine	400	3	29 July 2024
N-Nitroso-bisoprolol (2820170-76-9, NBP)	Bisoprolol	1500	4	24 August 2023
N-Nitroso-bumetanide (2490432-02-3, NNB)	Bumetanide	1500	4	24 August 2023
N-Nitroso-bupropion / N-tert-butyl-N-[1-(3-chlorophenyl)-1-oxopropan-2-yl]nitrous amide (2763780-10-3)	Bupropion	NMI		24 August 2023 Updated 4 February 2025
N-Nitroso-buspirone Impurity 1 / 2-(4-nitrosopiperazine-1-yl)-pyrimidine (872826-80-7)	Buspirone	400	3	15 October 2024
N-Nitroso-caspofungin / (10R,12S)-N-((2R,9S,11R,12S,14aS,15S,20S,25aS)-20-((R)-3-amino-1-hydroxypropyl)-12-((2-aminoethyl)(nitroso)amino)-23-((1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl)-2,11,15-trihydroxy-6-((R)-1-hydroxyethyl)-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2’,1’-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl)-10,12-dimethyltetradecanamide	Caspofungin	1500	4	29 July 2024
N-Nitroso-celiprolol	Celiprolol	1500	5	31 January 2024
N-Nitroso-cilazapril (1053740-92-3)	Cilazapril	1500	5	24 August 2023
N-Nitroso-cinacalcet	Cinacalcet	400	3	31 January 2024
1-(Diphenylmethyl)-4-nitrosopiperazine / 1-benzhydryl-4-nitrosopiperazine (1698-25-5)	Cinnarizine	400	3	29 July 2024
N-Nitroso-ciprofloxacin (864443-44-7)	Ciprofloxacin	NMI		24 August 2023 Updated 15 October 2024
N-Nitroso-N-desmethyl-clarithromycin / N-[(2S,3R,4S,6R)-2-[[(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-12,13-dihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxo-oxacyclotetradec-6-yl]oxy]-3-hydroxy-6-methyloxan-4-yl]-N-methylnitrous amide	Clarithromycin	NMI		29 July 2024
N-Nitroso-clozapine / 8-chloro-11-(4-methylpiperazin-1-yl)-5-nitroso-5H-dibenzo[b,e][1,4]diazepine (156632-03-0)	Clozapine	1500	5	24 April 2024
N-Nitroso-clozapine EP Impurity C / 8-chloro-11-(4-nitrosopiperazin-1-yl)-5H-dibenzo[b, e][1, 4]diazepine	Clozapine	400	3	24 April 2024
N-Nitroso-didecylamine	Colesevelam	100	2	4 February 2025
2,2,5-Trimethyl-3-nitroso-1,3-oxazolidine (77400-46-5, TMNO)	Cyanocobalamine	1500	4	24 April 2024
N-Nitroso-dabigatran etexilate (NDAB)	Dabigatran etexilate	1500		5 January 2023 Updated 24 August 2023 and 24 April 2024
5-Chloro-4-methyl-2-[(2S)-2-methyl-1-nitrosopyrrolidin-2-yl]-1H-benzimidazole (IDOR-1135-8758)	Daridorexant	1500	5	31 January 2024
N-Nitroso-N-deshydroxyethyl-dasatinib N-(2-chloro-6-methylphenyl)-2-((2-methyl-6-(4-nitrosopiperazin-1-yl)pyrimidin-4-yl)amino)thiazole-5-carboxamide (2135905-86-9)	Dasatinib	400	3	4 February 2025
N-Nitroso-desloratadine (1246819-22-6)	Desloratadine	400	3	24 August 2023
N-Nitroso-N-desmethyl dextromethorphan / (4bS,8aS,9S)-3-methoxy-11-nitroso-6,7,8,8a,9,10-hexahydro-5H-9,4b-(epiminoethano)phenanthrene (N-DEX)	Dextromethorphan	1500	4	29 July 2024
N-Nitroso-desmethyl-dimetindene / N-methyl-N-(2-(3-(1-(pyridin-2-yl)ethyl)-1H-inden-2-yl)ethyl)nitrous amide (NO-DDMT)	Dimetindene	18	1	15 October 2024
N-Nitroso-desmethyl-edoxaban / N1-(5-chloropyridin-2-yl)-N2-((1S,2R,4S)-4-(dimethylcarbamoyl)-2-(5-nitroso-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamido)cyclohexyl)oxalamide 4-methylbenzenesulfonate	Edoxaban	100	2	29 July 2024
N-Nitroso-desmethyl trimebutine	Trimebutine	1500	5	24 August 2023
N-Nitroso-trientine Impurity 1 / N-(2-aminoethyl)-N-(2-((2-aminoethyl)amino)ethyl)nitrous amide (2817316-41-7)	Trientine	18	1	29 July 2024
N-Nitroso-desmethylazithromycin	Azithromycin	NMI		24 August 2023
N-Nitroso-desmethyl-chloropyramine (N-DMCP)	Chloropyramine	18	1	24 August 2023
N-Nitroso-desmethyl-chlorphenamine / N-(3-(4-chlorophenyl)-3-(pyridin-2-yl)propyl)-N-methylnitrous amide	Chlorphenamine	18	1	4 February 2025
N-Nitroso-desmethyl-citalopram / N-(3-(5-cyano-1-(4-fluorophenyl)-1, 3-dihydroisobenzofuran-1-yl)propyl)-N-methylnitrous amide	Citalopram	100		31 January 2024 Updated 29 July 2024
N-Nitroso-desmethyl-tripelennamine	Tripelennamine	18	1	24 August 2023
N-Nitroso-desvenlafaxine	Desvenlafaxine	18	1	31 January 2024
N-Nitroso-diclofenac (66505-80-4)	Diclofenac	78000		24 August 2023 Updated 15 October 2024
N-Nitroso-diethanolamine (1116-54-7, NDELA)	-	1900		5 January 2023
N-Nitroso-diethylamine (55-18-5, NDEA)	-	26.5		15 September 2019
N-Nitroso-diisopropylamine / N,N-di(propan-2-yl)nitrous amide (601-77-4, DIPNA/NDIPA)	-	1500	5	15 September 2019 Updated 29 July 2024
N-Nitrosodiisopropanolamine / 1, 1'-(nitrosoimino)bis-2-propanol (53609-64-6)	-	400	3	24 April 2024
N-Nitroso-dimethylamine (62-75-9, NDMA)	-	96.0		15 September 2019
N-Nitroso-di-n-butylamine (924-16-3, NDBA)	-	26.5		20 July 2022
N-Nitroso-N-desmethyl-diphenhydramine / N-(2-benzhydryloxyethyl)-N-methylnitrous amide (55855-43-1)	Diphenhydramine / Dimenhydrinate	18	1	29 July 2024
N-Nitroso-diphenylamine (86-30-6, NDPh)	-	78000		5 January 2023
N-Nitroso-dipropylamine (621-64-7, NDPA)	-	26.5		20 July 2022
N-Nitroso-dorzolamide	Dorzolamide	1500		31 January 2024
N-Nitroso-duloxetine (2680527-91-5, NDLX)	Duloxetine	100		20 July 2022
N-Nitroso-desmethyl-eletriptan / 5-[2-(benzenesulfonyl)ethyl]-3-[[(2R)-1-nitrosopyrrolidin-2-yl]methyl]-1H-indole	Eletriptan	1500	4	4 February 2025
N-Nitroso-enalapril	Enalapril	1500	5	24 August 2023
N-Nitroso-epinephrine / N-nitroso-adrenaline	Epinephrine / Adrenaline	100	2	4 February 2025
N-Nitroso-esmolol	Esmolol	1500	4	31 January 2024
N-Nitroso-ethylisopropylamine / N-ethyl-N-propan-2-ylnitrous amide (16339-04-1, EIPNA/NEIPA)	-	400	3	15 September 2019 Updated 29 July 2024
N-Nitroso-felodipine	Felodipine	1500	5	24 August 2023
N-Nitroso-fenfluramine / N-ethyl-N-[1-[3-(trifluoromethyl)phenyl]propan-2-yl]nitrous amide (19023-40-6)	Fenfluramine	400	3	29 July 2024
N-Nitroso-flecainide / N-((1-nitrosopiperidin-2-yl)methyl)-2, 5-bis(2, 2, 2-trifluoroethoxy)benzamide (2901109-58-6)	Flecainide	1500	4	24 April 2024
N-Nitrosofluoxetine (150494-06-7)	Fluoxetine	100		5 January 2023
N-Nitroso-folic acid / 2-[[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methyl-nitrosoamino] benzoyl]amino]pentanedioic acid (26360-21-4, NFA)	Folic acid	1500	4	24 August 2023 Updated 29 July 2024
N-Nitroso-calcium folinate	Calcium folinate / Calcium levofolinate	NMI		31 January 2024
N-Nitroso-furosemide / 4-chloro-2-[furan-2-ylmethyl(nitroso)amino]-5-sulfamoylbenzoic acid (2708280-93-5)	Furosemide	1500		29 July 2024
N-Nitroso-desmethyl-galantamine / (4aS,6R,8aS)-3-methoxy-11-nitroso-4a,5,9,10,11,12-hexahydro-6H-benzo[2,3]benzofuro[4,3-cd]azepin-6-ol	Galantamine	18	1	4 February 2025
N-Nitroso-hydrochlorothiazide (63779-86-2, NHCTZ)	Hydrochlorothiazide	NMI		24 August 2023
N-Nitroso imatinib	Imatinib	1500	5	31 January 2024
Indapamide impurity A / 2-methyl-1-nitroso-2,3-dihydroindole (85440-79-5)	Indapamide	1500	5	31 January 2024
N-Nitroso-ethylenediamine-triacetic acid (862542-34-5)	Isosorbide mononitrate	1500	4	31 January 2024
N-Nitroso-iminodiacetic acid (25081-31-6)	Isosorbide mononitrate	1500	4	31 January 2024
N‐Nitroso‐ivacaftor / N-(2,4-di-tert-butyl-5-hydroxyphenyl)-1-nitroso-4-oxo-1,4-dihydroquinoline-3-carboxamide	Ivacaftor	1500	5	4 February 2025
N-Nitroso-ketamine / N-[1-(2-chlorophenyl)-2-oxocyclohexyl]-N-methylnitrous amide (86144-35-6)	Ketamine	1500	5	24 August 2023
N-Nitroso-labetalol (2820170-74-7)	Labetalol	1500	4	24 August 2023
N-Nitroso-landiolol	Landiolol	400	3	24 August 2023
N-Nitroso-leniolisib	Leniolisib	1500	5	31 January 2024
N-Nitroso-levofloxacin (1152314-62-9)	Levofloxacin	1500	4	24 August 2023
N-Nitroso-desethyllidocaine	Lidocaine / Lignocaine	100	2	31 January 2024
N-Nitroso-lisinopril / N2-((S)-1-carboxy-3-phenylpropyl)-N2-nitroso-L-lysyl-L-proline (519175-80-5, NLP)	Lisinopril	NMI		24 August 2023 Updated 29 July 2024
N-Nitroso-maprotiline / N-(3-(9, 10-dihydro-9, 10-ethanoanthracen-9-yl)propyl)-N-methylnitrous amide (204268-61-1)	Maprotiline	18	1	15 October 2024
N-Nitroso-masitinib / 4-[(4-nitrosopiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)-1,3-thiazol-2-yl]amino}phenyl)benzamide	Masitinib	400	3	24 April 2024
N-Nitroso-mefenamic acid (2114-63-8)	Mefenamic acid	78000		5 January 2023
N-Nitroso-iminodibenzyl / 10,11-dihydro-5-nitroso-5H-dibens[b,f]azepine / 2‐nitroso‐2‐azatricyclo[9.4.0.0³,⁸] pentadeca‐1(11),3(8),4,6,12,14‐hexaene) (7458-08-4)	Melipramin (Imipramine)	78000		15 October 2024
N-Nitroso-meropenem / (4R, 5S, 6S)-3-(((3S, 5S)-5-(dimethylcarbamoyl)-1-nitrosopyrrolidin-3-yl)thio)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid	Meropenem	1500	4	24 April 2024
N-Nitroso-methylphenidate (55557-03-4, NMPH)	Methylphenidate	1300		20 July 2022
N-Nitroso-ritalinic acid / 2-(1-nitrosopiperidin-2-yl)-2-phenylacetic acid	Methylphenidate	1500	4	24 April 2024
N-Nitroso-metoprolol (138768-62-4)	Metoprolol	1500	4	24 August 2023
N-Nitroso-mirabegron	Mirabegron	400	3	24 August 2023
N-(2-Hydroxy-2-phenylethyl)-N-(4-nitrophenethyl)nitrous amide / (R)-N-(2-hydroxy-2-phenylethyl)-N-(4-nitrophenethyl)nitrous amide (MBL-2-NO)	Mirabegron	400	3	29 July 2024
N-(4-Aminophenethyl)-N-(2-hydroxy-2-phenylethyl)nitrous amide / (R)-N-(4-aminophenethyl)-N-(2-hydroxy-2-phenylethyl)nitrous amide (MBL-3-NO)	Mirabegron	400	3	29 July 2024
N-Nitroso-mirtazapine	Mirtazapine	400	3	31 January 2024
N-Nitroso-morpholine (59-89-2, NMOR)	-	127.0		20 July 2022
N-Nitroso-moxifloxacin	Moxifloxacin	1500	4	24 August 2023
N-Nitroso-nor-oxycodone / (4R,4aS,7aS,12bS)-4a,9-dihydroxy-3-nitroso-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one	Nalmefene	1500	4	4 February 2025
N-Nitroso-nebivolol (1391051-68-5, NNEB)	Nebivolol	NMI		24 August 2023 Updated 31 July 2025
N-Nitroso-anabasine / 3-(1-nitrosopiperidin-2-yl)pyridine (37620-20-5, NAB)	Nicotine	1500	4	4 February 2025
N-Nitroso-anatabine / 3-[(2S)-1-nitroso-3,6-dihydro-2H-pyridin-2-yl]pyridine (71267-22-6, NAT)	Nicotine	1500	4	4 February 2025
N-Nitroso-nornicotine / 3-[(2S)-1-nitrosopyrrolidin-2-yl]pyridine (16543-55-8, NNN)	Nicotine	100		4 February 2025
N-Nitroso-nilotinib / 4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-(nitroso(4-(pyridin-3-yl)pyrimidin-2-yl)amino)benzamide (2925306-68-7)	Nilotinib	1500	5	4 February 2025
N-Nitroso desmethyl nintedanib	Nintedanib	400	3	31 January 2024
N-Nitroso-posaconazole Impurity 1 / 1-(4-(((3R,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methoxy)phenyl)-4-nitrosopiperazine	Posaconazole	400	3	29 July 2024
N-Nitroso-propafenone / N-(2-hydroxy-3-(2-(3-phenylpropanoyl)phenoxy)propyl)-N-propylnitrous amide	Propafenone	100	2	15 October 2024
N-Nitroso-N-ethyl-valaciclovir	Valaciclovir	400	3	24 August 2023
N-Nitroso-N-methyl-valaciclovir	Valaciclovir	400	3	24 April 2024
N-Nitroso-vibegron (S)-N-(4-(((2R,5S)-5-((R)-hydroxy(phenyl)methyl)-1-nitrosopyrrolidin-2-yl)methyl)phenyl)-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-6-carboxamide	Vibegron	1500	5	29 July 2024
N-Nitroso-N-methyl-4-aminobutyric acid / 4-[methyl(nitroso)amino]butanoic acid (61445-55-4, NMBA)	-	1500	4	15 September 2019 Updated 29 July 2024
N-Nitroso-N-methylaniline / N-methyl-N-phenylnitrous amide (614-00-6, NMPA)	-	100	2	31 January 2024
N-Nitroso-nortriptyline (55855-42-0, NNORT)	Amitriptyline, Nortriptyline	18	1	20 July 2022 Updated 15 October 2024
4-Nitroso-methyl piperazine-1-carboxylate (N-nitroso PMEC)	Omecamtiv mecarbil	400	3	29 July 2024
2-(4-Nitrosopiperazin-1-yl)ethanol (48121-20-6)	Opipramol	400	3	29 July 2024
N-Nitroso-paroxetine (2361294-43-9)	Paroxetine	1300		5 January 2023
N-Nitroso-p-chloro-benzylamino-pyridine (N-CBAP)	Chloropyramine	100	2	24 August 2023
N-Nitroso-perindopril	Perindopril	1500	5	24 August 2023
N-Nitroso-phenylephrine (78658-64-7)	Phenylephrine	100	2	24 August 2023
N-Nitroso-piperazine (5632-47-3, NPZ)	-	400	3	24 August 2023
N-Nitrosopiperidine (100-75-4)	-	1300		20 July 2022
N-Nitroso-pramipexole	Pramipexole	400	3	24 August 2023
N-Nitroso-propranolol (84418-35-9)	Propranolol	1500	4	24 August 2023
N-Nitroso-pseudoephedrine (1850-88-0)	Pseudoephedrine	1500	4	24 August 2023
N-Nitroso-pyrrolidine (930-55-2, NPYR)	-	1700		5 January 2023
N-Nitroso quetiapine HEEP impurity / 2-(2-(4-nitrosopiperazin-1-yl)ethoxy)ethan-1-ol (73486-81-4)	Quetiapine	1500		31 January 2024
N-Nitroso-quinapril	Quinapril	NMI		24 August 2023
N-Nitroso-ramipril	Ramipril	1500	5	24 August 2023
N-nitroso ranolazine impurity 1 / 1-(2-methoxyphenoxy)-3-(4-nitrosopiperazin-1-yl)propan-2-ol	Ranolazine	400	3	31 January 2024
N-Nitrosorasagiline (2470278-90-9)	Rasagiline	100	2	20 July 2022 Updated 24 August 2023
N-Nitroso-reboxetine	Reboxetine	127		24 August 2023
N-Nitroso-ribociclib impurity 1 / 7-cyclopentyl-N,N-dimethyl-2-((5-(4-nitrosopiperazin-1-yl)pyridine-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide	Ribociclib	400	3	31 January 2024
N-Nitroso-desformyl-riociguat / N-(4,6-diamino-2-(1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-5-yl)-N-methylnitrous	Riociguat	100	2	29 July 2024
N-Nitroso-2,4-thiazole amine / N-((2-isopropylthiazol-4-yl)methyl)-N-methylnitrous amide (NNTA)	Ritonavir	18	1	15 October 2024
N-Nitroso-rivaroxaban open-ring acid (S)-2-(2-((4-(5-((5-chlorothiophene-2-carboxamido)methyl)-2-oxooxazolidin-3-yl)phenyl)(nitroso)amino)ethoxy) acetic acid	Rivaroxaban	1500	4	31 January 2024
N-Nitroso-rivaroxaban amide / (S)-5-chloro-N-(2-hydroxy-3-(nitroso (4-(3-oxomorpholino)phenyl)amino) propyl)thiophene-2-carboxamide	Rivaroxaban	1500	4	31 January 2024
Rivaroxaban nitroso impurity 1 / N-(2-hydroxyethyl)-N-phenyl-nitrous amide (25413-76-7, N-Nitroso KCR-1)	Rivaroxaban	1500	4	29 July 2024
Rivaroxaban nitroso impurity 2 / N-(3-(1,3-dioxoisoindolin-2-yl)-2-hydroxypropyl)-N-(4-(3-oxomorpholino) phenyl)nitrous amide	Rivaroxaban	1500	4	29 July 2024
Rivaroxaban nitroso impurity 5 / N-(3-chloro-2-hydroxypropyl)-N-(4-(3-oxomorpholino)phenyl)nitrous amide (N-Nitroso RVR-A)	Rivaroxaban	1500	4	29 July 2024
N-Nitroso-desmethyl-rivastigmine / [3-[(1S)-1-[methyl(nitroso)amino] ethyl]phenyl] N-ethyl-N-methyl carbamate	Rivastigmine	100	2	15 October 2024
N-Nitroso-N-desmethyl-rizatriptan / N-(2-(5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indol-3-yl)ethyl)-N-methylnitrous amide	Rizatriptan	18	1	15 October 2024
N-Nitroso-salbutamol (2919946-71-5)	Salbutamol	1500	5	24 August 2023
N-Nitroso-sertraline	Sertraline	100	2	24 August 2023 Updated 16 October 2023 Updated 15 October 2024
N-Nitroso-desmethyl-sildenafil	Sildenafil	400	3	31 January 2024
N-Nitroso-silodosin / 1-(3-hydroxypropyl)-5-[(2R)-2-[nitroso-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]-2,3-dihydroindole-7-carboxamide	Silodosin	1500	4	24 April 2024
N-Nitroso-sotalol (134720-07-3)	Sotalol	1500	4	24 August 2023
N-Nitroso-desmethyl sumatriptan	Sumatriptan	18	1	31 January 2024
N-Nitroso-desmethyl-tamoxifen / (Z)-N-(2-(4-(1, 2-diphenylbut-1-en-1-yl)phenoxy)ethyl)-N-methylnitrous amide	Tamoxifen	18	1	24 April 2024
N-Nitroso-tamsulosin (2892260-31-8)	Tamsulosin	1500	4	20 July 2022 Updated 24 August 2023
N-Nitroso terazosin impurity C / N-nitroso 6,7-dimethoxy-2-(1-piperazinyl)-4-quinazolinamine / N-nitroso 2-(1-piperazinyl)-4-amino-6, 7-dimethoxyquinazoline	Terazosin	400	3	24 April 2024
N-Nitroso terazosin impurity N / (4-nitrosopiperazin-1-yl)(tetrahydrofuran-2-yl)methanone (2470438-57-2)	Terazosin	400	3	24 April 2024
N-Nitroso-desmethyl-terbinafine / (E)-N-(6,6-dimethylhept-2-en-4-yn-1-yl)-N-(naphthalen-1-ylmethyl)nitrous amide (NDT / NHNA)	Terbinafine	18	1	31 January 2024
N-Nitroso-terbinafine impurity A N-methyl-N-(napthalen-1-ylmethyl)nitrous amide (296760-88-8, NTA / NMNA)	Terbinafine	18	1	31 January 2024
N-Nitroso-terbinafine degradant N-[(2E)-6,6-dimethyl-2-hepten-4-yn-1-yl]-N-nitrosomethanamine (NTD / NHMA)	Terbinafine	18	1	31 January 2024
N-Nitroso-tetracaine	Tetracaine	400	3	31 January 2024
N‐Nitroso‐ticagrelor (2476859-55-7)	Ticagrelor	1500	5	31 January 2024
N-Nitroso-tigecycline / (4S, 4aS, 5aR, 12aS)-9-(2-(tert-butyl(nitroso)amino)acetamido)-4, 7-bis(dimethylamino)-3, 10, 12, 12a-tetrahydroxy-1, 11-dioxo-1, 4, 4a, 5, 5a, 6, 11, 12a-octahydrotetracene-2-carboxamide	Tigecycline	NMI		29 July 2024
N-Nitroso-desmethyl-tramadol / N-[[(1R,2R)-2-hydroxy-2-(3-methoxyphenyl)cyclohexyl]methyl]-N-methylnitrous amide	Tramadol	18	1	29 July 2024
N-Nitroso-trandolapril / (2S,3aR,7aS)-1-(N-((S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl)-N-nitroso-L-alanyl)octahydro-1H-indole-2-carboxylic acid	Trandolapril	1500	5	29 July 2024
N-Nitroso-trimetazidine (92432-50-3, NTMZ)	Trimetazidine	400	3	24 August 2023
N-Nitroso-urapidil	Urapidil	1500	4	31 January 2024
N-Nitroso-varenicline (2755871-02-2, NNV)	Varenicline	400	3	20 July 2022 Updated 16 October 2023
N-Nitroso-desvaleryl-valsartan / (S)-2-(((2'-(1H-tetrazol-5-yl)- [1,1′-biphenyl]-4-yl) methyl)(nitroso)amino)- 3-methylbutanoic acid (2254485-68-0)	Valsartan	NMI		29 July 2024
N-Nitroso-valsartan cyano-desvalerylmethylester / (S)-Methyl 2-(((2'-cyano-[1,1'-biphenyl]-4-yl)methyl)(nitroso) amino)-3-methylbutanoate	Valsartan	100	2	15 October 2024
N-Nitroso-vanzacaftor / (13S,Z)-26-(3-(2-(dispiro[2.0.24.13]heptan-7-yl)ethoxy)-1H-pyrazol-1-yl)-15,15-dimethyl-61,62-dihydro-5-thia-4,7-diaza-2(2,3),6(6,2)-dipyridina-1(1,3)-pyrrolidinacyclodecaphan-3-one 5,5-dioxide	Vanzacaftor	1500	4	15 October 2024
N-Nitroso-vildagliptin	Vildagliptin	1500	5	24 August 2023
N-Nitroso vildagliptin amide impurity / (S)-1-(2-(((1R, 3R, 5R, 7S)-3-hydroxyadamantan-1-yl)(nitroso)amino)acetyl)pyrrolidine-2-carboxamide	Vildagliptin	1500	5	15 October 2024
N-Nitroso-L-prolinamide / (S)-1-nitrosopyrrolidine-2-carboxamide (79108-51-3)	Vildagliptin	1500	4	4 February 2025
N-Nitroso-L-prolinenitrile / (S)-1-nitrosopyrrolidine-2-carbonitrile	Vildagliptin	1500	4	4 February 2025
N-Nitroso-vortioxetine	Vortioxetine	400	3	24 August 2023
N‐Nitroso‐desmethyl‐zolmitriptan / N-methyl-N-[2-[5-[[(4S)-2-oxo-1,3-oxazolidin-4-yl]methyl]-1H-indol-3-yl]ethyl]nitrous amide	Zolmitriptan	18	1	4 February 2025
2-(N-Nitrosomethylamino)-N-[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]acetamide (NNT)	Troriluzole	100	2	30 April 2025
N-Nitroso-sarcosine / 2-[methyl(nitroso)amino]acetic acid (13256-22-9, NSAR)	Troriluzole	1500	4	30 April 2025
N-Nitroso-vancomycin / (1S,2R,18R,19R,22S,25R,28R,40S)-48-[(2S,3R,4S,5S,6R)-3- [(2S,4S,5S,6S)-4-amino-5-hydroxy-4,6-dimethyloxan-2-yl] oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-22- (2-amino-2-oxoethyl)-5,15-dichloro-2,18,32,35,37-pentahydroxy-19- [[(2R)-4-methyl-2-[methyl(nitroso)amino]pentanoyl]amino] -20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentazaoctacyclo[26.14.2.23,6.214,17.18, 12.129,33.010,25.034,39]pentaconta-3,5,8(48),9,11,14,16,29(45),30,32,34(39),35,37,46,49-pentadecaene-40-carboxylic acid (155386-25-7)	Vancomycin	1500	4	30 April 2025
N-Nitroso-N-desmethyl-mianserin / 2-nitroso-1,2,3,4,10,14b-hexahydrodibenzo[c,f]pyrazino[1,2-a]azepine	Mianserin	400	3	30 April 2025
N-Nitroso-desmethyl-lercanidipine / 3-(1-((3,3-diphenylpropyl)(nitroso)amino)-2-methylpropan-2-yl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	Lercanidipine	100	2	30 April 2025
N-Nitroso-desmethyl-lercanidipine impurity C / 3-(1-((3,3-diphenylpropyl)(nitroso)amino)-2-methylpropan-2-yl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate	Lercanidipine	100	2	30 April 2025
N-Nitroso-dasatinib / N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)(nitroso)amino)thiazole-5-carboxamide	Dasatinib	1500	5	30 April 2025
N-Nitroso-dalbavancin / (2S,3S,4R,5R,6S)-6-[[(1S,2R,19R,22R,34S,37R,40R,52R) -5,32-dichloro-52-[3-(dimethylamino)propylcarbamoyl] -2,26,31,44,49-pentahydroxy-22-[methyl(nitroso)amino] -21,35,38,54,56,59-hexaoxo-47-[(2R,3S,4S,5S,6R)-3,4, 5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-7,13,28- trioxa-20,36,39,53,55,58-hexazaundecacyclo [38.14.2.23,6.214,17.219,34.18,12.123,27.129,33.141, 45.010,37.046,51]hexahexaconta-3,5,8,10,12(64),14(63),15,17(62),23(61),24,26,29(60),30,32,41 (57),42,44,46(51),47,49,65-henicosaen-64-yl]oxy]-3,4-dihydroxy-5-(10-methylundecanoylamino)oxane-2-carboxylic acid	Dalbavancin	1500	4	30 April 2025
N-Nitroso-desmethyl-cabergoline / (6aR,9R,10aR)-7-allyl-N-(ethylcarbamoyl)-N-(3-(methyl(nitroso)amino)propyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide	Cabergoline	18	1	30 April 2025

CPCA: Carcinogenic Potency Categorisation Approach
NMI: Non mutagenic impurity should be controlled to ICH Q3A and ICH Q3B guideline limits

Acceptable Intake (AI) Limit to be applied to maximum daily dose (MDD) of the drug product. These limits are applicable only if a product contains a single N-nitrosamine.
Potential presence of nitrosamine impurities with structures derived from drug substances or their related impurities. This does not mean that the impurity will be found in all products or pharmaceutical forms containing the drug substance. Please refer to EMA's Q&A on the risk factors for the presence of nitrosamines for details.

Nitrosamine structures are available print version

TGA Established acceptable intakes for other nitroso-structures in medicines [PDF, 1.03 MB]

TGA Established acceptable intakes for other nitroso-structures in medicines [Word, 1.2 MB]

Product types