Lynch KL, Dominy SS, Graf J, et al. Detection of levamisole exposure in cocaine users by liquid chromatography-tandem mass spectrometry

Department of Laboratory Medicine, University of California San Francisco, San Francisco, California 94110, USA.
Journal of analytical toxicology (Impact Factor: 2.86). 04/2011; 35(3):176-8. DOI: 10.1093/anatox/35.3.176
Source: PubMed


Levamisole, a veterinary antihelminthic, was recently recognized as an adulterant in cocaine and is known to cause severe adverse reactions in some cocaine users. Because of the health concerns involving levamisole-adulterated cocaine, we developed a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the detection of levamisole in urine. This method was used to determine the prevalence of levamisole in cocaine-positive patient samples. All cocaine-positive urine samples that were sent to the San Francisco General Hospital Clinical Laboratory were tested for levamisole for one month. For LC, an Agilent 1200 series was used with a C(18) column and a gradient of mobile phase A (0.05% formic acid) and B (acetonitrile/methanol). Detection was carried out with an Applied Biosystems QTRAP(®) LC-MS-MS. The levamisole LC-MS-MS method was linear over the range of 5-2500 ng/mL (r > 0.996). Interassay and intraassay CVs were < 6%. The lower limit of detection for levamisole was 0.5 ng/mL. Out of 949 total urine drug screens, 20% were positive for benzoylecgonine, and of those, 88% were positive for levamisole. The high prevalence of levamisole-adulterated cocaine and potential toxicity in cocaine users is a serious public health concern. These findings validate the utility of an LC-MS-MS method for the detection of levamisole.

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    ABSTRACT: Most of the illicit cocaine consumed in the United States and elsewhere is contaminated with levamisole, a veterinary medication. Agranulocytosis caused by levamisole exposure through cocaine abuse was first described in 2009. Since then, levamisole has also been shown and is known to cause vascular and neurologic complications. In this review, we provide an overview of the medical consequences of exposure to levamisole from adulterated cocaine. Within the past year, several new case series have deepened our understanding of the levamisole-agranulocytosis vasculopathy syndrome. The common nature of this exposure has been delineated, cocaine contaminated with levamisole. Significant controversy surrounds the role of granulocyte colony stimulating factor (GCSF) in levamisole-associated agranulocytosis. More than three fourths of cocaine users in the United States are exposed to levamisole; a significant minority of these individuals will develop autoimmune-mediated neutropenia, cutaneous vascular complications, and/or leukoencephalopathy. Levamisole exposure should be considered in the differential diagnosis of patients who present with these conditions in the setting of cocaine abuse. Neutropenia appears to resolve rapidly with cessation of exposure, so that GCSF therapy and a work-up for other causes may not be needed in all patients.
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    ABSTRACT: Levamisole is an immunomodulatory agent that was used to treat various cancers before being withdrawn from the United States market in 2000 because of adverse effects. Levamisole is currently approved as an antihelminthic agent in veterinary medicine, but is also being used illicitly as a cocaine adulterant. Potential complications associated with use of levamisole-laced cocaine include neutropenia, agranulocytosis, arthralgias, retiform purpura, and skin necrosis. Treatment is primarily supportive, and skin lesions typically resolve with cessation of cocaine use. The incidence of hospitalizations related to use of levamisole-contaminated cocaine continues to increase and clinicians should be aware of the more common clinical manifestations.
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