USP Publishes New Chapter on Adulteration of Dietary Supplements with
Drugs and Drug Analogs
Reviewed: Proposed USP Chapter
2251: Adulteration of
Dietary Supplements with Drugs and Drug Analogs.
The sale of active pharmaceutical
ingredients (APIs) masquerading as dietary supplements is a major issue in the
United States and worldwide. These products contain highly bioactive
pharmaceutical compounds that may or may not have undergone safety or efficacy
testing, and may be present at a wide variety of concentration levels.
Therefore, products that contain APIs but are illegally labeled to be a dietary
supplement pose a potentially serious health risk to the unsuspecting consumer.
The proposed chapter in the United States Pharmacopeia (USP) recognizes
three health categories as particularly susceptible to this kind of fraud:
products marketed for sexual enhancement, weight loss, and athletic performance
enhancement.
USP recommends analyzing
questionable ingredients or products initially with a non-targeted method,
which is a method where the target analyte is not known. Non-targeted methods
include those where a large number of molecules can be detected, e.g., an
HPLC-UV/MS or NMR analysis.
The largest part of the chapter is devoted
to methods for the detection of phosphodiesterase 5 (PDE5) inhibitors, such as
sildenafil, tadalafil, and vardenafil – drugs sold for erectile dysfunction.
The chapter ends with a list and chemical structures of known PDE5 inhibitors
and the proposed non-targeted methods to detect these drugs and their
derivatives, including HPLC-UV, HPLC-MS, HPTLC-UV (or alternatively with
visible or MS detection), MS, NMR, and a bioassay.
Comment: The proposed new USP chapter has been
published in the Pharmacopeial Forum,1 and was open for public
comments until July 31, 2015. The goal is to provide the tools to help
manufacturers in the detection of APIs added to botanical ingredients and
finished products and to facilitate the screening for undeclared drugs.
However, the detection of such ingredients, in particular with regard to PDE5
inhibitors, resembles a cat-and-mouse game, since new sildenafil-derivatives
that can elude detection by targeted analytical methods are created on a
regular basis. While being a serious health issue, and a main area of US FDA
enforcement action (there have been 15 product recalls in the United States
between April 2015 and July 2015 due to APIs sold as dietary supplements), the
problem with drugs labeled as dietary supplements is not the main focus of the
ABC-AHP-NCNPR Botanical Adulterants Program since these products are in essence
mislabeled and therefore illegal drugs rather than dietary supplements. The
frequent use of “dietary supplement” and the intended placement of the chapter
in the Dietary Supplements section of the USP, possibly allowing people to
infer that the products containing APIs are dietary supplements rather than misbranded drugs, were also issues raised during the
public comment period.2
Reference
1.
Bzhelyansky
A. <2251> Adulteration of dietary supplements with drugs and
drug analogs. Pharmacopeial Forum. 2015;41(3).
2.
McGuffin M. AHPA Comments on
Proposed <USP 2251>. Letter to the United States Pharmacopeia. July 31,
2015. Available at: http://www.ahpa.org/Portals/0/pdfs/AHPA-Comments-USP-2251.pdf. Accessed October
7, 2015.
