NDMA Analyzer

Can you "check" your product?

The inclusion of nitrosamines, a carcinogenic substance, in pharmaceuticals and recycled water is now a worldwide problem. In Japan, the Ministry of Health, Labour and Welfare (MHLW) announced in 2022 the “Voluntary Inspection of the Risk of Contamination of Nitrosamines in Pharmaceutical Products,” and the related industries are in need of measurement results of nitrosamines.

What are nitrosamines?
Substance confirmed to be carcinogenic in 1957 and classified as a “carcinogen” by the World Health Organization (WHO) and others in 2015.

What are the regulations in Japan?
(1) Pharmaceuticals (2021)

MHLW notified of voluntary inspection regarding risk of contamination.
Scope of application: Contractors involved in the manufacture and supply of medicines and their packaging, containers, etc.

(2) Tap water (2009)

Announcement from the Ministry of Health, Labour and Welfare that it plans to consider setting water quality control targets following the WHO drinking water guidelines.

(3) Other ministries are focusing on food, water environment, and air quality, and are gathering information and investigating the dangers.

What is the allowable amount of contamination or inclusion?
Tolerable intake announced by the Ministry of Health, Labor and Welfare, there are 9 types in total, N-Nitrosodimethylamine (NDMA), N-Nitrosomorpholine (NMOR)

What products are contaminated?
Pharmaceuticals, foods, cosmetics, daily necessities, etc.

Do other countries regard as a problem with this substance?
Guidelines have been published by the U.S. (FAD), Europe (EMA), Health Canada, etc.

Dedicated analyzer for nitrosamines that enables short-time measurement

Nichiri Manufacturing Co. has started contract analysis of nitrosamines, and sales of analyzers dedicated for nitrosamines are started. Its features are (1) no sample concentration process required, (2) short measurement time (approximately 20 minutes/measurement), (3) high sensitivity (several ng/L), and (4) small sample volume (20 to 200 μL/measurement), making it a revolutionary instrument that reduces cost and time in fields where frequent measurements are required. This measurement principle employs the "HPLC-PR-CL method," which has been operated, researched, and evaluated in the U.S. based on this principle, and its high usefulness has been reported.

No sample concentration process required

The system incorporates an anion eliminator (AEM) developed by our company, which has two effects: (1) it creates basic conditions suitable for detection, and (2) it removes impurities (ionic substances) originating from the sample, This device has the twofold effect of removing impurities (ionic substances) derived from the sample. As a result, the instrument can achieve very high sensitivity (sub-ng/L), eliminating the need for a concentration process.

Short time measurement (approx. 20 min/measurement)

Existing measurement methods for "N-nitrosamines" require a concentration operation (pretreatment) as much as 1000 times using 250 to 1000 mL of sample water. This eliminates the pretreatment process and allows for quick measurement.

High sensitivity measurement (several ng/L)

Nitrosamines such as NDMA are converted to components with strong oxidizing power by UV irradiation. When mixed with a luminol solution that selectively reacts with this oxidizing component, a chemiluminescence reaction occurs, and this light can quantify 1 ng/L of NDMA, enabling high-sensitivity measurement.

Small volume sample (20 to 200 μL/measurement)

Cost savings for frequent measurement fields To measure ng/L levels with existing methods, samples of 1L or more are concentrated 1000-fold by solid-phase extraction using activated carbon, and then GC-MS/MS or LC-MS/MS, which are sophisticated and expensive analytical instruments, are used. While extremely long time and manpower are required for the measurement, this system allows saving both time and cost by eliminating the need for a concentration process.

Principle of Measurement

Associate Professor Hitoshi Kodamaya of Kagoshima University focused on the fact that NDMA decomposes and produces peroxynitrite (ONOO-) by UV irradiation. He developed an analytical method for NDMA (N-nitrosamines) that combines a luminol chemiluminescence detection method capable of ultra-sensitive detection of peroxynitrite and UV irradiation (highly sensitive detection method for nitrosamines (HPLC-PR-CL method)). This is combined with our developed technology, Anion Elimination Equipment (AEM), which is the measurement principle of this device, the "dedicated measuring device for nitrosamines. Associate Professor Kodamaya's development of the analysis method was the result of joint research with the U.S. Water Treatment Agency (OCWD) and a professor at Nagasaki University. 　The following is the research report.

Research report based on the measurement principle

H. Kodamatani, S. L. Roback, M. H. Plumlee, K. P. Ishida, H. Masunaga, N. Maruyama, T. Fujioka, An inline ion-exchange system in a chemiluminescence-based analyzer for direct analysis of N-nitrosamines in treated wastewater, J. Chromatogr. A, 1553 (2018) 51-56

Publications

・H. Kodamatani, K. Sugihara, T. Tanisue, R. Kanzaki, T. Tomiyasu, Contamination, Decomposition, and Formation of N-Nitrosodimethylamine in Water Samples at the ng/L Level of Determination, Anal. Sci. (2020) 36, 1393-1399 ・H. Kodamatani, T. Tanisue, T. Fujioka, R. Kanzaki, T. Tomiyasu, Inhibitory effect of alkyl groups on N-nitrosamine formation from secondary and tertiary alkylamines with monochloramine, Environmental Technology & Innovation, 22 (2021) 101520 ・S. L. Roback, H. Kodamatani, T. Fujioka, M. H. Plumlee, Validation of a novel direct-injection chemiluminescence-based method for N-nitrosamine analysis in advanced-treated recycled water, drinking water, and wastewater, Environ. Sci.: 　　Water Res. Technol., (2020) 6, 1106-1115