scholarly journals Analysis of Crowdsourced Metformin Tablets from Individuals Reveals Widespread Contamination with N-Nitrosodimethylamine (NDMA) in the United States

2020 ◽  
Author(s):  
Qian Wu ◽  
Evgenia Kvitko ◽  
Amber Jessop ◽  
Shannon Williams ◽  
Ryan C. Costantino ◽  
...  
Keyword(s):  
United States ◽  
High Resolution Mass Spectrometry ◽  
Daily Intake ◽  
The United States ◽  
Product Recalls ◽  
Acceptable Daily Intake ◽  
Drug Products ◽  
Post Market ◽  
United States Food ◽  
States Food

AbstractRecent reports of metformin drug products contaminated with unacceptable levels of the probable human carcinogen N-Nitrosodimethylamine (NDMA) prompted a national sampling of post-market metformin drug products. To most broadly sample the market and minimize supply chain bias, metformin medication samples were crowdsourced directly from individuals across many states in the United States. 128 samples were received, and liquid chromatography-high resolution mass spectrometry tests for a panel of nitrosamines revealed significant levels of NDMA that trend with labeling company. 42% of all medication samples contained detectable levels of NDMA and, when scaled to maximum daily tablet dose, 36% of all medication samples contained NDMA levels exceeding the FDA daily acceptable intake limit. The highest NDMA detection from the tested samples was 1565 ng per tablet, which, when commonly taken four times a day, is 65 times the United States Food and Drug Administration (FDA) acceptable daily intake limit. Results underscore the need for immediate product recalls of tainted medications and an overall investigation of metformin manufacturing practices.

scholarly journals A Broadly Accessible Liquid Chromatography Method for Quantification of Six Nitrosamine Compounds and N,N-Dimethylformamide in Metformin Drug Products Using High Resolution Mass Spectrometry

2020 ◽  
Author(s):  
Qian Wu ◽  
Evgenia Kvitko ◽  
Nicola Zenzola ◽  
Kaury Kucera ◽  
David Light
Keyword(s):  
High Resolution Mass Spectrometry ◽  
The United States ◽  
High Mass ◽  
Chromatography Method ◽  
Drug Products ◽  
Regulatory Guidance ◽  
High Mass Resolution ◽  
United States Food ◽  
States Food ◽  
Liquid Chromatography Method

N-nitrosodimethylamine (NDMA) and the industrial solvent, N,N-dimethylformamide (DMF), are both probable human carcinogens that have been detected in pharmaceutical drug products like metformin, which is used to treat type II diabetes. Some lots of metformin drug products have exceeded the United States Food and Drug Administration (FDA) daily allowable intake limit for NDMA, while the presence of DMF has been detected at several orders of magnitude higher than NDMA. A recent study found that a low abundance isotope of DMF interferes with NDMA quantification by using a unique subset of LC-MS instruments capable of high mass resolution. In this study, an LC-HRMS method is developed that chromatographically separates NDMA from DMF in metformin drug products to eliminate interference. The method can detect nitrosamines and DMF under the current regulatory guidance for industry and provides a solution for simultaneously quantifying nitrosamines and DMF for a broad range of LC-MS instruments.

scholarly journals A Broadly Accessible Liquid Chromatography Method for Quantification of Six Nitrosamine Compounds and N,N-Dimethylformamide in Metformin Drug Products Using High Resolution Mass Spectrometry

2020 ◽  
Author(s):  
Qian Wu ◽  
Evgenia Kvitko ◽  
Nicola Zenzola ◽  
Kaury Kucera ◽  
David Light
Keyword(s):  
High Resolution Mass Spectrometry ◽  
The United States ◽  
High Mass ◽  
Chromatography Method ◽  
Drug Products ◽  
Regulatory Guidance ◽  
High Mass Resolution ◽  
United States Food ◽  
States Food ◽  
Liquid Chromatography Method

N-nitrosodimethylamine (NDMA) and the industrial solvent, N,N-dimethylformamide (DMF), are both probable human carcinogens that have been detected in pharmaceutical drug products like metformin, which is used to treat type II diabetes. Some lots of metformin drug products have exceeded the United States Food and Drug Administration (FDA) daily allowable intake limit for NDMA, while the presence of DMF has been detected at several orders of magnitude higher than NDMA. A recent study found that a low abundance isotope of DMF interferes with NDMA quantification by using a unique subset of LC-MS instruments capable of high mass resolution. In this study, an LC-HRMS method is developed that chromatographically separates NDMA from DMF in metformin drug products to eliminate interference. The method can detect nitrosamines and DMF under the current regulatory guidance for industry and provides a solution for simultaneously quantifying nitrosamines and DMF for a broad range of LC-MS instruments.

scholarly journals Differentiation between the Regulatory paths placed on Mouthwashes in the US and EU

2018 ◽  
Vol 6 (2) ◽  
pp. 8-13
Author(s):  
Philip Saddik ◽  
John Pappan
Keyword(s):  
United States ◽  
The United States ◽  
The European Union ◽  
Oral Diseases ◽  
External Appearance ◽  
Regulatory Systems ◽  
The Us ◽  
United States Food ◽  
States Food ◽  
Therapeutic Properties

Regulating oral rinses has been and still is a topic of debate and confusion. Oral rinses are products that are mainly used for cleaning, perfuming and changing the appearance of the teeth, which in turn improves the individual’s external appearance. Adding medicinal ingredients to these rinses, it can then be used for the elimination and/or prevention of some oral diseases, an example being gingivitis. The United States Food and Drug Administration placed guidelines which state that mouthwashes with possible therapeutic properties should be registered as drugs rather than cosmetics. Meanwhile, on a different continent, Germany along with the other members of the European Union decided not to categorize mouthwashes as drugs, but rather as cosmetics, using its sole purpose of cleaning and beautifying the teeth as the excuse. The following research will thoroughly differentiate between the diverse regulatory systems forced upon mouthwashes across the two countries—the United States and Germany.

Program planning with Tobit analysis—the United States food stamp case

1980 ◽  
Vol 14 (2) ◽  
pp. 91-95
Author(s):  
J.E. Epperson ◽  
M.R. Holmes ◽  
C.L. Huang ◽  
W.K. Scearce
Keyword(s):  
United States ◽  
Program Planning ◽  
The United States ◽  
Food Stamp ◽  
Tobit Analysis ◽  
United States Food ◽  
States Food

Abbreviated New Drug Application Process: A Gift for The Industry and The Patients

2021 ◽  
pp. 331-335
Author(s):  
Hindustan Abdul Ahad ◽  
Haranath Chinthaginjala ◽  
Gangireddy Jayasimha Reddy ◽  
Pasupuleti Dheeraj Krishna ◽  
Syed Rahamathulla ◽  
...  
Keyword(s):  
Drug Application ◽  
The United States ◽  
New Drugs ◽  
Brand Name ◽  
Application Process ◽  
Drug Products ◽  
Federal Food ◽  
United States Food ◽  
States Food ◽  
New Drug Application

The United States Food and Drug Administration (USFDA) is one of the main regulated agencies wherein the submission and approval of the new drugs is done. This review is based on the process of submission to the ANDA as per FDA norms as described in paragraph IV submission in Federal Food, Drug, and Cosmetic Act (FD and C Act). No drug would exist in the market until it gets accepted by regulatory authorities. The ANDA submission is for those firms seeking to copy branded drugs before running out of patents to get profit on them. A generic applicant must provide in its application a "certification" that a patent submitted to FDA by the brand-name drug's sponsor and scheduled in FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (the Orange Book). A Generic Product must meet the standards recognized by FDA in Reference listed drugs (RLD). This study concludes the process of ANDA submission to FDA and acts correlated to the submission in paragraph IV, the details of ANDA filling in the eCTD format and overview of the review process the checklist to the applicant.

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