RAMAN
Introduction
The counterfeiting of commercial products such as clothing
items, hand bags, and movies is an ever-increasing worldwide
problem. However, the risk to the public health from purchas-
ing a counterfeit hand bag is minimal compared to the risk associated
with a consumer purchasing and consuming a counterfeit pharmaceu-
tical product. The increase in the counterfeiting of pharmaceutical
drugs worldwide is of major concern to the Food and Drug
Administration (FDA) [1].
Counterfeit pharmaceuticals pose a significant public health and
safety risk since they may contain harmful impurities, may be inef-
fective, and/or have low to no bioavailability. Counterfeit pharma-
ceuticals may include products that may have the correct ingredients,
wrong ingredients, incorrect quantities of the active pharmaceutical
ingredients (API), as well as fake packaging. Evidence analyzed by
the FDA’s Forensic Chemistry Center (FCC) submitted as part of
counterfeit investigations has included pharmaceuticals, dietary sup-
plements, cosmetics, and even medical devices. In recent cases, well-
organized counterfeiters have become more sophisticated in both the
manufacture and distribution of the counterfeit product. Therefore,
where many of these counterfeit products were previously found and
purchased on the black market and the internet, they are now finding
their way into the legal distribution chain [2]. In countries outside the
U.S., drug counterfeiting is widespread, and in some cases, may
account for more than 50 % of the products sold in those markets [1].
The number of counterfeit investigations conducted by the FDA’s
Office of Criminal Investigation (OCI) has increased from five per
year in the late 1990’s to over 20 per year since 2000 [1]. The FDA’s
Forensic Chemistry Center (FCC) provides forensic analysis of evi-
dence collected as part of OCI’s counterfeit investigations. The type
of analysis the FCC performs on suspect counterfeit products
includes screening or rapid analysis of products to sort legitimate
product from suspect counterfeit products. The screening of suspect
counterfeit products also generates chemical information which can
be used to determine the potential public health risk. Additionally, the
FCC may generate forensic information related to the source or ori-
gin of a counterfeit product, for example, how do similar counterfeits
relate to each other?
The FCC uses a wide range of analytical methods and instrumental
techniques in the screening and sourcing of suspect counterfeit and
adulterated pharmaceuticals. An instrumental technique used fre-
quently in the analysis of suspect counterfeit product evidence is
Raman spectroscopy. Raman spectroscopy is used to perform a vari-
ety of analyses in the pharmaceutical industry, as well as in forensic
analysis [3,4,5,6,7,8,9]. The vibrational spectroscopic information
obtained from a forensic sample using Raman spectroscopy is com-
plimentary to the infrared (IR) spectroscopic information that may be
obtained for the same forensic sample. However, the inherent instru-
mental and sampling advantages of Raman versus IR spectroscopy in
some cases, makes Raman a better choice in the analysis of counter-
feit and suspect adulterated pharmaceuticals [3,4,5].
Raman spectroscopy provides specific information on the identifi-
cation of analytes, characterization of sample matrices, and molecu-
lar spectroscopic information useful in the structural elucidation of
unknowns [3,4]. The technique is rapid and when coupled with sam-
ple preparation methodologies (i.e., micro-extractions, fraction col-
lections, small particle analysis), a large amount of information can
be obtained from a single piece of forensic evidence.
This paper focuses specifically on the Raman spectroscopic analy-
sis of suspect counterfeit tablets as an example, although the same
sample preparations and Raman spectroscopic measurements can be
applied to suspect counterfeit capsule formulations and to adulterated
pharmaceutical products.
Experimental
All Raman spectra presented and discussed in this paper were col-
lected on a research grade dispersive Raman spectrometer system
with both micro- and macro-sampling capabilities. The Raman spec-
1
American Pharmaceutical Review
The Use of Raman
Spectroscopy in the
Detection of Counterfeit
and Adulterated
Pharmaceutical Products
Mark R. Witkowski, Ph.D.
FDA Forensic Chemistry Center
