Analytical methods for the detection of undeclared synthetic drugs in traditional herbal medicines as adulterants Jamshed Haneef, a Mohammad Shaharyar, a Asif Husain, a Mohd Rashid, a * Ravinesh Mishra, a Nadeem A. Siddique b and Manoj Pal c Traditional herbal medicines (THMs) are gaining popularity worldwide as an alternative approach to prescription drugs for many reasons including a general perception that they are safe. But recently there have been number of reported studies that reveal adulteration of THMs with undeclared synthetic drugs, which may potentially cause serious toxic adverse effects. This paper reviews the various classes of synthetic drugs that were found to be adulterated in THMs worldwide. The main focus is to highlight newer analytical tools used to detect adulteration. Due to the advancement in hyphenated techniques like liquid chromatography tandem mass spectrometry (LC-MS/MS), gas chromatography-tandem mass spectrometry (GC-MS/MS) and other conventional tools, it has become possible to detect synthetic drugs and their structural analogues as adulterants even if they are present in small quantities. This review also gives an overview of health-related risks after consuming such spurious products and challenges for future perspectives to control such type of malpractices. Copyright © 2013 John Wiley & Sons, Ltd. Keywords: traditional herbal medicines (THMs); adulterants; hyphenated techniques; adulteration; analytical methods; undeclared synthetic drugs Introduction Traditional herbal medicines (THMs) are widely used globally because of their claim to be entirely natural alternatives, their affordability, and a general perception that they are safe. In contrast to prescription drugs, herbal medicines are perceived as safe and harmless due to their natural origin. Recently, there have been reports that these herbal medicines were found adul- terated with undeclared synthetic drugs or their structurally mod- ified analogues. [1–4] Adulteration, as defined by Miller et al., is ‘the addition of an impure or inferior component not ordinarily part of that substance or removal of a crucial entity usually used to imply that a substance is debased (desecrated) as a result’. [5] Intentional adulteration, deliberate contamination often occurs when the necessary natural substances are in short supply or expensive or when the supplier intends to intensify a specific pharmaco- logic effect. [6] THMs are herbal preparations containing active ingredients of plants, or other plant materials, or combinations thereof. THM often serves as one component of a comprehensive system of medicine that may involve the use of plant-, animal-, and mineral-based medicines to prevent and treat illnesses. They are used in most countries in the world, and have been relied on to support, promote, retain, and regain human health. According to the World Health Organization (WHO) up to 80% of people living in developing countries still rely primarily on traditional medicines for their healthcare [48] (Figure 1). The use of THM in industrialized countries is also spreading rapidly, where herbal medicines are often referred to as alternative medicines or com- plementary medicines or even as herbal dietary supplements (Figure 2). WHO and the United States Dietary Supplements Health and Education Act (DSHEA) of 1994 both define dietary supplements as a product (other than tobacco) that is meant to supplement the diet. Both organizations include vitamins, minerals, herbs, botanical products, amino acids, or dietary substances in their definitions. [48] Systems of THM that are widely used in national healthcare systems around the world include traditional Ayurvedic medicine, traditional Chinese medicine, traditional Unani medicine, traditional western herbal medicine, traditional Japanese Kampo medicine and traditional Tibetan Buddhist medicine. Traditional medicines are characterized in many different ways throughout the var- ious jurisdictions around the world. They are commonly sold either as a prescription or over-the-counter (OTC) medicine or as self-medication. Although THM has long been used, there is little knowledge regarding its safety and efficacy among the user. [49,50] THMs are not well regulated and are freely available from health-food stores, in supermarkets, and on the Internet. Due to poor regulation, THMs are prone to contamination [8] and adulteration with undeclared synthetic drugs. [7] However several guidelines by WHO play an impor- tant role in monitoring the safety of herbal drugs and * Correspondence to: Mohd Rashid, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India. E-mail: rashidpharm2008@gmail.com a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, 110062, India b Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, 110062, India c Department of Chemistry, Indian Institute of Technology (IIT), Haridwar, Uttarakhand, Roorkee, 247667, India Drug Test. Analysis 2013, 5, 607–613 Copyright © 2013 John Wiley & Sons, Ltd. Review Drug Testing and Analysis Received: 8 April 2012 Revised: 20 January 2013 Accepted: 11 March 2013 Published online in Wiley Online Library: 7 May 2013 (www.drugtestinganalysis.com) DOI 10.1002/dta.1482 607