Intoxication with 3-MeO-PCP alone: A case report and literature review.

RATIONALE: 3-Methoxyphencyclidine (3-MeO-PCP) is a new psychoactive substance derived from phencyclidine. Although it can lead to severe intoxications, the main manifestations and optimal management have not been well characterized. Here, we report 2 cases of 3-MeO-PCP intoxication in the same patient, and summarize the manifestations of this intoxication reported in literature. PATIENT CONCERNS: A 17-year-old male purchased a bag of 3-MeO-PCP on the Internet but took an oral dose (200 mg) that corresponds to the less active isomer 4-MeO-PCP. He developed high blood pressure (158/131 mm Hg), tachycardia (100 bpm), and neurological manifestations (confusion, hypertonia, nystagmus, and then agitation). A maculopapular rash appeared, although this may have been related to the administration of midazolam. Hyperlactatemia (2.6 mmol/L) was the main laboratory finding. Seven days later, he returned to the emergency department after sniffing 50 mg of 3-MeO-PCP. High blood pressure, tachycardia, and neurological manifestations (psychomotor impairment and dysarthria) were present but less severe than after the first intoxication. DIAGNOSIS: In the first intoxication, the blood and urine 3-MeO-PCP concentrations were, respectively, 71.1 ng/mL and 706.9 ng/mL. Conventional toxicity tests were all negative. In the second intoxication, biological samples were not available. INTERVENTIONS: In the first intoxication, treatment consisted of intravenous hydration and midazolam. The patient was transferred to an intensive care unit for monitoring. After the second intoxication, he was monitored for 12 hours. OUTCOMES: The patient's condition improved quickly in both cases. LESSONS: These cases provide additional information on the manifestations of 3-MeO-PCP intoxication. These manifestations are mainly cardiovascular (high blood pressure, tachycardia) and neurological. The fact that second (50 mg) intoxication was less severe than the first (200 mg) is suggestive of a dose-effect relationship for 3-MeO-PCP. The first case also emphasizes the risk of dosing errors caused by the similarity between the names "3-MeO-PCP" and "4-MeO-PCP."

Metabolites to parent 3-MeO-PCP ratio in human urine collected in two fatal cases.

In this article, two fatal cases related to the use of 3-methoxyphencyclidine (3-MeO-PCP) are described. This compound is a new psychoactive substance that belongs to the phencyclidine family. In the recent period, this dissociative drug has gained interest because of its proposal as a legally available alternative to phencyclidine in some countries. The scientific literature related to 3-MeO-PCP is very poor. Using standard ultra-performance liquid chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry, the authors focused on the detection of 3-MeO-PCP and its metabolites in human urine. 3-MeO-PCP metabolism was studied in vitro after drug incubation with human liver microsomes and the identified metabolites were investigated in the urine of the two forensic cases. 3-MeO-PCP metabolites, including O-demethyl-3-MeO-PCP, piperidine-hydroxy-3-MeO-PCP, O-demethyl-piperidine-di-hydroxy-3-MeO-PCP and piperidine-di-hydroxy-3-MeO-PCP, were detectable in the urine from both cases and the ratio between metabolites and parent 3-MeO-PCP, always lower than 1, were calculated to estimate the proportionality of metabolites. At this stage, one can conclude that testing for 3-MeO-PCP metabolites does not increase the window of detection of the drug.

False-positive phencyclidine (PCP) on urine drug screen attributed to desvenlafaxine (Pristiq) use.

We report a likely false-positive phencyclidine (PCP) result detected with a urine drug screen (UDS) (Medtox, St Paul, Minnesota, USA) in the setting of therapeutic desvenlafaxine (Pristiq) use. Desvenlafaxine (O-desmethylvenlafaxine) is the active metabolite of venlafaxine (Effexor). Prior reports have confirmed venlafaxine use resulting in a false-positive for PCP on a UDS. However, there has been a paucity of reporting of commercially available desvenlafaxine formulations (Pristiq, Khedezla) resulting in false-positives for PCP on a UDS.

Two Cases of Non-fatal Intoxication with a Novel Street Hallucinogen: 3-Methoxy-Phencyclidine.

3-Methoxy-phencyclidine (3-MeO-PCP) is a structural derivative of the dissociative hallucinogen phencyclidine (PCP). Although PCP toxicity is well documented, little is known about this new psychoactive substance despite being available on the black market even in central Europe. The objective of this case report is to present clinical and laboratory data of analytically confirmed non-fatal intoxication of two subjects with 3-MeO-PCP. A preliminary assessment of potential metabolites excreted into urine was enabled using the liquid chromatography high resolution mass spectrometric method.

New Psychoactive Substances 3-Methoxyphencyclidine (3-MeO-PCP) and 3-Methoxyrolicyclidine (3-MeO-PCPy): Metabolic Fate Elucidated with Rat Urine and Human Liver Preparations and their Detectability in Urine by GC-MS, "LC-(High Resolution)-MSn" and "LC-(High Resolution)-MS/MS".

BACKGROUND: 3-Methoxyphencyclidine (3-MeO-PCP) and 3-methoxyrolicyclidine (3-MeOPCPy) are two new psychoactive substances (NPS). The aims of the present study were the elucidation of their metabolic fate in rat and pooled human liver microsomes (pHLM), the identification of the cytochrome P450 (CYP) isoenzymes involved, and the detectability using standard urine screening approaches (SUSA) after intake of common users' doses using gas chromatography-mass spectrometry (GC-MS), liquid chromatography-multi-stage mass spectrometry (LC-MSn), and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS). METHODS: For metabolism studies, rat urine samples were treated by solid phase extraction or simple precipitation with or without previous enzymatic conjugate cleavage. After analyses via LC-HR-MSn, the phase I and II metabolites were identified. RESULTS: Both drugs showed multiple aliphatic hydroxylations at the cyclohexyl ring and the heterocyclic ring, single aromatic hydroxylation, carboxylation after ring opening, O-demethylation, and glucuronidation. The transferability from rat to human was investigated by pHLM incubations, where Odemethylation and hydroxylation were observed. The involvement of the individual CYP enzymes in the initial metabolic steps was investigated after single CYP incubations. For 3-MeO-PCP, CYP 2B6 was responsible for aliphatic hydroxylations and CYP 2C19 and CYP 2D6 for O-demethylation. For 3-MeO-PCPy, aliphatic hydroxylation was again catalyzed by CYP 2B6 and O-demethylation by CYP 2C9 and CYP 2D6 Conclusions: As only polymorphically expressed enzymes were involved, pharmacogenomic variations might occur, but clinical data are needed to confirm the relevance. The detectability studies showed that the authors' SUSAs were suitable for monitoring the intake of both drugs using the identified metabolites.

Definitive Drug and Metabolite Screening in Urine by UPLC-MS-MS Using a Novel Calibration Technique.

Drug screening is an essential analytical tool for detection of therapeutic, illicit and emerging drug use. Presumptive immunoassay screening is widely used, while initial definitive testing by chromatography-coupled mass spectrometry is hampered due to complex pre-analysis steps, long chromatography time and matrix effects. The aim of this study is to develop and validate a definitive test for rapid and threshold accurate screening of 33 drugs or metabolites (analytes) in urine. Sample preparation in a 96-well plate format involves rapid glucuronidase hydrolysis followed by dilution, filtration and ultra-performance liquid chromatography-MS-MS analysis. Chromatographic separation, on an ACQUITY UPLC® BEH phenyl column is optimized for a 3-min MS-MS ion acquisition. Matrix effect was normalized by an innovative technique called threshold accurate calibration employing an additional analysis with an analyte spike as an internal standard undergoing the same matrix effect as an analyte in a drug-positive donor specimen. Accuracy and precision, at above and below threshold concentrations, were determined by replicate analysis of control urine pools containing 50, 75, 125 and 150% of threshold concentrations. Accuracy and selectivity were further demonstrated by concordant findings in proficiency and confirmatory testing. The study shows the applicability of definitive testing as an alternative to immunoassay screening and demonstrates a new approach to normalization of matrix effect.

Do trauma patients with phencyclidine-positive urine drug screens have increased morbidity or mortality?

BACKGROUND: Phencyclidine (PCP) use is anecdotally associated with agitation and injury and is frequently tested for in the setting of trauma. We sought to determine characteristics of trauma patients with a PCP-positive urine immunoassay drug screen (UDS) and if they had increased levels of care or mortality. METHODS: A 5-year retrospective review of a level 1 trauma center's trauma registry identified patients with a PCP-positive UDS. This group was then compared with 2 randomly selected control groups from the same trauma registry which were matched for age and sex but differed in that one had no sEtOH detected and a negative UDS (drug-free group) whereas the other had sEtOH or an other-than-PCP-positive UDS (other-drug group). Subgroup analysis was performed comparing PCP-positive patients with undetectable sEtOH with other-drug patients with undetectable sEtOH. RESULTS: The registry contained 7770 patients of which 156 met inclusion criteria. The mean age was 33.4years (range, 19-63), and 77% were male (n=121). When compared with the other-drug group, the PCP-positive group had significantly lower injury severity score, rates of intensive care unit admission, and sEtOH. No difference was seen in vital signs, mechanism of injury, ventilator days, intensive care unit days, total hospital days, disposition, or mortality between the 3 groups. This remained true even when subgroups with negative sEtOH were compared. CONCLUSION: This study suggests that a PCP-positive UDS in the setting of trauma is not associated with increased level of care, length of stay, or mortality.

Phencyclidine analog use in Sweden--intoxication cases involving 3-MeO-PCP and 4-MeO-PCP from the STRIDA project.

BACKGROUND: 3-Methoxy-phencyclidine (3-MeO-PCP) and 4-methoxy-phencyclidine (4-MeO-PCP) are analogs of and drug substitutes for the dissociative substance PCP ("Angel dust"), a recreational drug that was most popular in the 1970s. In Sweden, use of methoxylated PCP analogs was noted starting in mid-2013, according to statistics from the Poisons Information Centre. The objective of this case series was to present clinical and bioanalytical data from analytically confirmed non-fatal intoxications associated with 3-MeO-PCP and/or 4-MeO-PCP within the STRIDA project. STUDY DESIGN: Observational case series of consecutive patients with self-reported or suspected exposure to new psychoactive substances (NPS) and who require hospital care. PATIENTS AND METHODS: Blood and urine samples were collected from intoxicated patients presenting at emergency departments (ED) or intensive care units (ICU) all over Sweden. NPS analysis was performed by multicomponent liquid chromatographic-tandem mass spectrometric (LC-MS/MS) and LC-high-resolution MS (LC-HRMS) methods. Data on clinical features were collected during Poisons Information Centre consultations and retrieved from medical records. RESULTS: The Poisons Information Centre registered its first call related to methoxylated PCP analogs in July 2013, while analytically confirmed cases first appeared in October 2013. From July 2013 to March 2015, 1243 cases of suspected NPS intoxication originating from ED or ICU were enrolled in the STRIDA project. During the 21-month period, 56 (4.5%) patients tested positive for 3-MeO-PCP and 11 (0.9%) for 4-MeO-PCP; 8 of these cases involved both substances. The 59 patients were aged 14-55 (median: 26) years and 51 (86%) were men. Co-exposure to other NPSs and/or classical drugs of abuse was common with only 7 cases (12%) indicated to be 3-MeO-PCP single-substance intoxications; prominent clinical signs seen in the latter cases were hypertension (systolic blood pressure ≥ 140 mmHg; 7 cases), tachycardia (≥ 100/min; 5 cases), and altered mental status (4 cases) including confusion, disorientation, dissociation, and/or hallucinations. Mixed-drug users displayed not only the same clinical features, but also more sympathomimetic effects including agitation (38%) and dilated pupils (33%). Patients testing positive for 3-/4-MeO-PCP were typically under medical care for 1-2 days (85%), and 37% of all cases were graded as severe intoxications (Poisoning Severity Score 3). Besides standard supportive therapy, 49% of the patients were treated with benzodiazepines and/or propofol. CONCLUSION: Laboratory analysis constitutes an important basis for the assessment of NPS hazard and availability. The adverse effects noted in cases of acute intoxications involving 3- and/or 4-MeO-PCP resembled those of other dissociatives such as PCP, ketamine, and methoxetamine. However, similar to intoxications involving other NPS, poly-substance use was found to be common.

Oral fluid for the detection of drugs of abuse using immunoassay and LC-MS/MS.

The utility of oral fluid as a sample matrix for the analysis of drugs has been increasing in popularity over the last few years. This is largely because of collection advantages over other matrices, but also due to the rapid improvements in analytical assays including highly sensitive liquid reagent format enzyme immunoassays and LC-MS/MS. This review will highlight improvements in assay formats, sensitivity, laboratory equipment and sample processing using low sample volumes to expand drug test profiles.

How often do false-positive phencyclidine urine screens occur with use of common medications?

BACKGROUND: Previous reports describe false-positive urine immunoassay screens for phencyclidine (PCP) associated with use of tramadol, dextromethorphan, or diphenhydramine. The likelihood of these false positives is unknown. OBJECTIVE: We sought to find the relative frequency of false-positive PCP screens associated with these medications and to look for any other medications with similar associations. METHODS: In an IRB-approved study, we retrospectively reviewed charts of all ED encounters with positive urine screens for PCP in our hospital from 2007 through 2011, inclusive. Urine samples were tested for drugs of abuse using the Siemens Syva EMIT II Immunoassay. Our laboratory routinely confirmed all positive screens using GC-MS with results classified as either "confirmed" (true positive) or "failed to confirm" (false positive). We recorded all medications mentioned in the chart as current medications or medications given before the urine sample. We used Fisher's exact test to compare frequencies of tramadol, dextromethorphan, diphenhydramine, and other medications between the two groups. RESULTS: Tramadol, dextromethorphan, alprazolam, clonazepam, and carvedilol were significantly more frequent among the false-positive group, but the latter three were also associated with polysubstance abuse. Diphenhydramine was more frequently recorded among the false-positive group, but this was not statistically significant. CONCLUSION: False-positive urine screens for PCP are associated with tramadol and dextromethorphan and may also occur with diphenhydramine. Positive PCP screens associated with alprazolam, clonazepam, and carvedilol were also associated with polysubstance abuse.

Creatinine normalization of workplace urine drug tests: does it make a difference?

BACKGROUND: This study examines the effect of creatinine normalization on urine drug concentrations of 5 substances (amphetamines, cocaine, marijuana, opiates, and phencyclidine) and how this affects the proportion of reported positives. METHODS: The Wilcoxon matched-pairs signed-ranks test was used to compare the mean prenormalization urinary drug concentration with the mean postnormalization urinary drug concentration. Frequency analysis was performed on dichotomous drug test results and the information was used to complete McNemar testing for each drug to determine the difference of proportions for prenormalization positive drug tests to postnormalization positive drug test. RESULTS: Each drug tested (N = 4460) was found to have a statistically significant increase in mean urinary drug concentration after creatinine normalization with effect sizes ranging from small to medium with cocaine having the largest effect size (r = 0.229) and phencyclidine having the lowest effect size (r = 0.121). The differences in proportion of dichotomous results between study and control groups for drugs tested were compared with the McNemar test. Each drug had a statistically significant (P = 0.0010) increase of positive drug tests. CONCLUSIONS: This result indicates that specimen dilution does affect the number of laboratory-positive results confirmed.

Dispersive liquid-liquid microextraction prior to field-amplified sample injection for the sensitive analysis of 3,4-methylenedioxymethamphetamine, phencyclidine and lysergic acid diethylamide by capillary electrophoresis in human urine.

A novel capillary zone electrophoresis (CZE) with ultraviolet detection method has been developed and validated for the analysis of 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD) and phencyclidine (PCP) in human urine. The separation of these three analytes has been achieved in less than 8 min in a 72-cm effective length capillary with 50-µm internal diameter. 100 mM NaH(2)PO(4)/Na(2)HPO(4), pH 6.0 has been employed as running buffer, and the separation has been carried out at temperature and voltage of 20°C, and 25kV, respectively. The three drugs have been detected at 205 nm. Field amplified sample injection (FASI) has been employed for on-line sample preconcentration. FASI basically consists in a mismatch between the electric conductivity of the sample and that of the running buffer and it is achieved by electrokinetically injecting the sample diluted in a solvent of lower conductivity than that of the carrier electrolyte. Ultrapure water resulted to be the better sample solvent to reach the greatest enhancement factor. Injection voltage and time have been optimized to 5 kV and 20s, respectively. The irreproducibility associated to electrokinetic injection has been correcting by using tetracaine as internal standard. Dispersive liquid-liquid microextraction (DLLME) has been employed as sample treatment using experimental design and response surface methodology for the optimization of critical variables. Linear responses were found for MDMA, PCP and LSD in presence of urine matrix between 10.0 and 100 ng/mL approximately, and LODs of 1.00, 4.50, and 4.40 ng/mL were calculated for MDMA, PCP and LSD, respectively. The method has been successfully applied to the analysis of the three drugs of interest in human urine with satisfactory recovery percentages.