DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



N-nitrosamines as "special case" leachables in a metered dose inhaler drug product.

Author(s): Norwood DL, Mullis JO, Feinberg TN, Davis LK

Affiliation(s): Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Rd., P.O. Box 368, Ridgefield, CT 06877-0368, USA. daniel.norwood@boehringer-ingelheim.com

Publication date & source: 2009-07, PDA J Pharm Sci Technol., 63(4):307-21.

Publication type: Research Support, Non-U.S. Gov't

N-nitrosamines are chemical entities, some of which are considered to be possible human carcinogens, which can be found at trace levels in some types of foods, tobacco smoke, certain cosmetics, and certain types of rubber. N-nitrosamines are of regulatory concern as leachables in inhalation drug products, particularly metered dose inhalers, which incorporate rubber seals into their container closure systems. The United States Food and Drug Administration considers N-nitrosamines (along with polycyclic aromatic hydrocarbons and 2-mercaptobenzothiazole) to be "special case" leachables in inhalation drug products, meaning that there are no recognized safety or analytical thresholds and these compounds must therefore be identified and quantitated at the lowest practical level. This report presents the development of a quantitative analytical method for target volatile N-nitrosamines in a metered dose inhaler drug product, Atrovent HFA. The method incorporates a target analyte recovery procedure from the drug product matrix with analysis by gas chromatography/thermal energy analysis detection. The capability of the method was investigated with respect to specificity, linearity/range, accuracy (linearity of recovery), precision (repeatability, intermediate precision), limits of quantitation, standard/sample stability, and system suitability. Sample analyses showed that Atrovent HFA contains no target N-nitrosamines at the trace level of 1 ng/canister.

Page last updated: 2010-10-05

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017