3 Things to Know About Ni­tros­ami­nes

For­t­u­na­te­ly, drug scan­dals do not oc­cur too of­ten. Ho­we­ver, the re­cent dis­co­very of ni­tros­ami­nes in car­dio­vas­cu­lar ta­blets has gar­ne­red a lot of at­ten­ti­on. The po­ten­ti­al­ly car­ci­no­ge­nic sub­s­tance had been unkno­wing­ly en­te­ring the bo­dies of pa­ti­ents for ye­ars, caus­ing gre­at con­cern among the po­pu­la­ti­on. It is the­r­e­fo­re im­portant to take a clo­ser look at this che­mi­cal sub­s­tance (or ra­ther, group of sub­s­tances).

1) What are Ni­tros­ami­nes?

Ni­tros­ami­nes, spe­ci­fi­cal­ly N‑nitrosamines, are a lar­ge group of or­ga­nic com­pounds that are stron­gly car­ci­no­ge­nic (as shown in ani­mal stu­dies). They are for­med when ni­tri­te re­acts with ni­tro­sata­ble ami­nes. The best-known ni­tros­ami­nes in­clude ni­tro­so­dime­thyl­ami­ne (NDMA), ni­tro­so­pyr­ro­li­di­ne (NPYR), and ni­tro­so­di­ethyl­ami­ne (NDEA). NDMA has re­cei­ved a lot of at­ten­ti­on in re­cent ye­ars as it was found in the afo­re­men­tio­ned me­di­ca­ti­on (Ra­nit­i­di­ne) and led to its re­call. It was for­med as a re­sult of ch­an­ges in the pro­duc­tion pro­cess of the blood pres­su­re-lo­we­ring ta­blets and re­main­ed un­de­tec­ted for a long time, as ni­tros­ami­nes are not vi­si­ble du­ring the stan­dard qua­li­ty con­trol of phar­maceu­ti­cal com­pa­nies.

2) Whe­re do Ni­tros­ami­nes oc­cur in ever­y­day life?

Ni­tros­ami­nes can be for­med in va­rious ways in foods and other samples. For ex­am­p­le, they can be for­med th­rough the pro­ces­sing of ni­tri­te-con­tai­ning me­ats and fish at high tem­pe­ra­tures, espe­ci­al­ly du­ring gril­ling or fry­ing. Ni­tros­ami­nes can also be for­med from ni­tra­te and ni­tri­te ad­di­ti­ves in foods that are used as pre­ser­va­ti­ves. To­b­ac­co smo­ke is an­o­ther com­mon source of ni­tros­ami­nes. Ni­tros­ami­nes can also be for­med in our di­ges­ti­ve pro­cess due to the aci­dic sto­mach en­vi­ron­ment re­sul­ting from a re­ac­tion bet­ween ni­tra­te and ami­nes.

Ni­tros­ami­nes can also be found in cos­me­tics and pro­ducts made from rub­ber, such as la­tex mat­tres­ses or bal­loons. The oc­cur­rence in in­dus­tri­al­ly ma­nu­fac­tu­red pro­ducts is usual­ly sub­ject to strict con­trols, and if they are con­ta­mi­na­ted with ni­tros­ami­nes, this must be in­di­ca­ted. For ex­am­p­le, some bal­loons should only be in­fla­ted with a pump for this re­ason. The in­ta­ke th­rough food can be re­du­ced by fry­ing at lower tem­pe­ra­tures and avo­i­ding ni­tra­te- and ni­tri­te-con­tai­ning pro­ducts.

3) How are Ni­tros­ami­nes me­a­su­red?

Com­mon scree­ning me­thods in the phar­maceu­ti­cal in­dus­try for qua­li­ty con­trol in­clude the se­pa­ra­ti­on of sub­s­tances by HPLC in com­bi­na­ti­on with an elec­tro­spray (ESI) or at­mo­sphe­ric pres­su­re che­mi­cal io­niza­ti­on (APCI) and a mass spec­tro­me­ter for the de­ter­mi­na­ti­on of the re­spec­ti­ve sub­s­tances. Al­ter­na­tively, gas chro­ma­to­gra­phy can also be used in com­bi­na­ti­on with EI and a mass spec­tro­me­ter. Ho­we­ver, the very vo­la­ti­le NDMA po­ses a ma­jor chall­enge for test­ing la­bo­ra­to­ries. Some com­mon­ly used sol­vents in the phar­maceu­ti­cal in­dus­try have the same mass as NDMA (so-cal­led iso­ba­ric com­pounds) and are the­r­e­fo­re dif­fi­cult to se­pa­ra­te and de­tect. The­re is thus a gre­at need for re­se­arch in this area to pro­tect people’s he­alth.

Read our App Note Ul­tra-Sen­si­ti­ve GC-SICRIT®-HRMS Ana­ly­sis of Ni­tros­ami­nes in Phar­maceu­ti­cal Samples fea­turing Hy­dro­gen as GC Car­ri­er Gas and Shi­madzu LCMS-9030 QToF“ in the down­load sec­tion on our web­site to learn how our SICRIT® ion source can make a small con­tri­bu­ti­on in this re­se­arch area and to fu­ture drug safe­ty.