Faster Test Reported for Detecting Fake Tamiflu in Fight Against Counterfeit Drugs

Newswise — Chemists in Georgia are reporting development of a fast new method to detect fake Tamiflu, the mainstay medication for preventing and treating bird flu. Tamiflu has become a target for counterfeiters as recent outbreaks of bird flu have increased public demand for supplies of just-in-case antiviral drugs to use in case of an epidemic of the deadly disease.

In a report scheduled for presentation here today at the 235th national meeting of the American Chemical Society, Facundo M. Fernandez, Ph.D., and colleagues describe use of a method called Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) that can determine authenticity of large batches of Tamiflu samples up to 20 times faster than conventional methods.

"It's a one-step process that doesn't require any extensive sample preparation," said Fernandez, of the Georgia Institute of Technology. Using DESI-MS, analysis of the Tamiflu powder yields results in less than one minute. The "gold standard" for gauging pharmaceutical quality control is a powerful but much slower method called high performance liquid chromatography (HPLC), he said. Analysis by HPLC could take up to an hour.

The researchers describe their study as the first successful demonstration of DESI-MS's use for Tamiflu screening. "This method is really targeted at screening large amounts of products" that might be expected during a pandemic of influenza, Fernandez said. "In case of a crisis, you wouldn't be able to wait an hour per sample. You'd want to screen hundreds of samples per day."

When fears of a pandemic, a global epidemic, of avian influenza first emerged, worried consumers in the United States and other countries began to horde Tamiflu in 2005, seeking prescriptions from physicians and purchasing the medication from online pharmacies. In 2007, there were 86 confirmed human cases of bird flu in the world, according to the World Health Organization. The fatality rate was high, with 59 deaths.

Fernandez tested DESI-MS's effectiveness by collecting different Tamiflu samples from online pharmacies and found all of them to contain the active ingredient. Customers who purchase from online pharmacies, he warns, should use extra caution when shopping. Although some online pharmacies are certified, he says people usually look for low prices instead. "What you get online can be pretty much anything," he said. "It's very easy for the counterfeiter to bypass the system that's in place to protect the consumer. And it's very easy for the consumer to get medications."

At $6.50 per pill, Tamiflu's high cost and demand have made it a preferred target for fakes, Fernandez noted. Counterfeits have already surfaced in Chicago, San Francisco and other areas.

International trade in counterfeits is a lucrative enterprise — and an increasingly sophisticated one, Fernandez said. According to the International Chamber of Commerce, global trade in counterfeit goods costs the U.S. economy between $200 billion and $250 billion a year in lost sales and is responsible for the loss of more than 750,000 American jobs. "The penalties for counterfeiting pharmaceuticals are much lower than for trafficking illegal drugs like cocaine," Fernandez said. "Many of the operations focused on making illegal drugs are shifting to counterfeiting drugs because of the low penalties and high profits."

A few initiatives have surfaced to fight the presence of fakes, including ones by the U. S. Food and Drug Administration and the WHO, among others. Global awareness has increased, Fernandez said, but it's not enough. "What's the percentage of fake drugs in the marketplace? I don't know. I don't think anybody can give you a real number. That's really a huge problem."

Fernandez remains optimistic about solving the problem of fake Tamiflu, however. "I think it's possible to shut down this traffic, but it will require new tools and new approaches," he said. "We need to get very creative because the incentive for making fake drugs is huge. We always feel like we're trying to catch up with the counterfeiters. Every time we get a new batch of fakes, they're more sophisticated than the previous batch."

The American Chemical Society — the world's largest scientific society — is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

Note for reporters' use only: For full information about the New Orleans meeting, including access to abstracts of more than 9,000 scientific papers and hundreds of non-technical summaries, visit http://www.eurekalert.org/acsmeet.php. A poster on this research, CHED 255, will be presented at 11:00 a.m., Monday, April 7, in the Morial Convention Center, Hall A, during the symposium "Undergraduate Research Poster Session: Analytical Chemistry."

Facundo M. Fernandez, Ph.D., is an Assistant Professor in the School of Chemistry and Biochemistry at Georgia Institute of Technology in Atlanta, Georgia. ALL PAPERS ARE EMBARGOED UNTIL DATE AND TIME OF PRESENTATION, UNLESS OTHERWISE NOTED CHED 255Consecutive reaction monitoring desorption electrospray ionization mass spectrometry for rapid authentication of potentially counterfeit Tamiflu capsules Program Selection: Division of Chemical EducationTopic Selection: Undergraduate Research Poster Session: Analytical Chemistry

Kristin Johnson1, Leonard Nyadong1, Michael Green2, and Facundo M. Fernandez1. (1) School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, (2) Division of Parasitic Diseases, National Center for Infectious Diseases, Center for Disease Control and Prevention, Atlanta, GA 30333 Abstract The recent outbreak of avian influenza has increased the demand for antivirals. Tamiflu®, the leading antiviral on the market, has become a target for counterfeiters. Reports of counterfeit Tamiflu have already appeared thus creating an urgent need for rapid and sensitive Tamiflu® authentication tools. Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) with consecutive reaction monitoring (CRM) is presented as a selective and rapid method to screen Tamiflu capsules with minimal sample preparation. DESI-MS analysis of genuine Tamiflu® gives predominantly the protonated monomer and dimer adducts. Doping the spray solution with crown ether gives a 1:1 protonated complex with the crown ether. MS2 analysis of this complex gives the protonated oseltamivir monomer which can be fragmented with MS3 to give the ion m/z 225. Monitoring this ion by reactive DESI creates a highly selective tool to screen oseltamivir. Screening of Tamiflu® samples collected over the internet showed that all samples contained oseltamivir. ________________________________________Researcher Provided Non-Technical Summary Briefly explain in lay language what you have done, why it is significant and what are its implications (particularly to the general public)

The counterfeiting of pharmaceuticals is a well-recognized public health problem. There have been many alarming reports of counterfeit antimalarials, antibiotics, steroids, analgesics, anti-asthma and anti-allergy drugs. Due to the recent outbreaks of avian influenza, which could lead to an influenza pandemic, the demand for antivirals has increased tremendously with stockpiling leading to shortage of supply. With Tamiflu® as the leading antiviral in the market, its high cost ($6.50 per pill) and demand, have made it a preferred target for counterfeiters. Reports of counterfeit Tamiflu samples which do not contain the active ingredient (oseltamivir) have already appeared. This thus leads to an urgent need for a rapid and sensitive authentication and screening tool for Tamiflu capsules. In this study Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) was used to rapidly screen Tamiflu capsules with minimal sample preparation. This method provides a high-throughput alternative to quickly analyze the authenticity of counterfeit drugs.

How new is this work and how does it differ from that of others who may be doing similar research?

DESI-MS has been applied to other pharmaceuticals such as antimalarials, and it has been used for related applications. However, DESI-MS has never before been used for the screening of Tamiflu, and this method is a highly sensitive and quick way to determine the authenticity of this important drug with very little sample preparation.