Xylazine intoxication in humans and its importance as an emerging adulterant in abused drugs: A comprehensive review of the literature.

Xylazine is not a controlled substance; it is marketed as a veterinary drug and used as a sedative, analgesic and muscle relaxant. In humans, it could cause central nervous system depression, respiratory depression, bradycardia, hypotension, and even death. There have been publications of 43 cases of xylazine intoxication in humans, in which 21 (49%) were non-fatal scenarios and 22 (51%) resulted in fatalities. Most of the non-fatal cases required medical intervention. Over recent years xylazine has emerged as an adulterant in recreational drugs, such as heroin or speedball (a cocaine and heroin mixture). From the 43 reported cases, 17 (40%) were associated with the use of xylazine as an adulterant of drugs of abuse. Its chronic use is reported to be associated with physical deterioration and skin ulceration. Literature shows some similar pharmacologic effects between xylazine and heroin in humans. These similar pharmacologic effects may create synergistic toxic effects in humans. Therefore, fatalities among drug users may increase due to the use of xylazine as an adulterant. Xylazine alone has proven harmful to humans and even more when it is combined with drugs of abuse. A comprehensive review of the literature of non-fatal and fatal xylazine intoxication cases including those in which the substance was used as adulterant is presented, in order to increase the awareness in the forensic community, law enforcement, and public health agencies.

Simultaneous determination of xylazine, free morphine, codeine, 6-acetylmorphine, cocaine and benzoylecgonine in postmortem blood by UPLC-MS-MS.

Xylazine, a veterinary sedative, has been found as an adulterant of heroin in street drugs in Puerto Rico. It was found in combination with free morphine and 6-acetylmorphine, codeine, cocaine and benzoylecgonine in postmortem cases at the Puerto Rico Institute of Forensic Sciences (PRIFS). Xylazine is not approved for human use because it has been proven harmful. Currently, three separate analyses are required to determine all the aforementioned drugs at the PRIFS's toxicology laboratory. To reduce analysis time consumption, sample volume, run time, sample preparation and cost, a high-throughput ultra-high-pressure liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of xylazine, free morphine, 6-acetylmorphine, codeine, cocaine and benzoylecgonine in 0.25 mL postmortem blood by protein precipitation, fulfilling confirmation criteria with three transitions for each compound with acceptable relative ion intensities. Linearity was established between 10-1,000 ng/mL. Total run time was 2.5 min. Limit of detection was 1 ng/mL for cocaine and xylazine, 2 ng/mL for 6-acetylmorphine and 10 ng/mL for free morphine, codeine and benzoylecgonine. The intra-day and inter-day precision and accuracy was less than 15.6%. Process efficiencies ranged from 35.9 to 123.4% and recoveries from 59.9 to 110.1%. The developed method was successfully applied to casework.