Two methods have been developed and validated according to GMP standards:
HS-GC-QQQ-MS,
N-nitroso-dimethyl-amine-D6, N-nitroso-diethyl-amine-D10, N-nitroso-diisopropyl-amine-D14 and N-nitroso-dibuthyl-amine-D18 are used as internal standards.
The method is validated for the following volatile compounds on HS-GC-QQQ-MS:
| N-nitroso-dimethyl-amine | NDMA | CAS No.: 62-75-9 |
| N-nitroso-N-methylethyl-amine | NMEA | CAS No.: 10595-95-6 |
| N-nitroso-diethyl-amine | NDEA | CAS No.: 55-18-5 |
| N-nitroso-N-ethyl-isopropyl-amine | NEIPA/EIPNA | CAS No.: 16339-04-1 |
| N-nitroso-diisopropyl-amine | NDIPA/DIPNA | CAS No.: 601-77-4 |
| N-nitroso-di-n-propyl-amine | NDPA/DPNA | CAS No.: 621-64-7 |
| N-nitroso-di-n-butyl-amine | NDBA/DBNA | CAS No.: 924-16-3 |
HPLC-QQQ-MS,
4-nitroso-piperazine-D8 and/or N-nitroso-dimethyl-amine-D10 and/or N-nitroso-pyrrolidine-D8 are used as internal standards.
The method is validated for the following non-volatile compounds on HPLC-QQQ-MS:
| N-nitroso-pyrrolidine | NPyr | CAS No.: 930-55-2 |
| N-nitroso-piperazine | NPipA | CAS No.: 5632-47-3 |
| N-nitroso-morpholine | NMor | CAS No.: 59-89-2 |
| N-nitroso-piperidine | NPip | CAS No.: 100-75-4 |
| N-nitroso-N-methyl-4-aminobutyric acid | NMBA | CAS No.: 61445-55-4 |
| N-methyl-N-nitroso-piperazine | MeNP/NMNPipA | CAS No.: 16339-07-4 |
| N-nitroso-N-methylaniline | MNPA/PMNA | CAS No.: 614-00-6 |
QL: 0.1-25 µg/component/matrix (0.1-25 ppb)
Amounts needed for analysis (may differ if maximal daily dose is higher)
| Analytics | API/Solvent | Product |
| Verification | 2,5 grams, 5 ml. | 15 grams, 50 tablets, 50 ml. |
|
Test |
2,5 grams, 5 ml. | 5 grams, 15 tablets, 5 ml. |