The mobile phase consisted of 0. The flow rate was 0. The capillary voltage was set to 2. System operation and data acquisition were controlled using the Mass Lynx 4. A representative chromatogram is presented in Figure 1. Left panel represents the lowest quality control sample with concentrations of 0.
Right panel is an authentic sample with concentrations of 0. The correlation coefficient was above 0. LOQ samples of 0. Within-assay CVs were estimated by analysis of 10 separate replicates of quality control QC samples at three concentrations 0.
Between-assay CVs were determined by analysis of aliquots of each QC concentration at 10 different days, one replicate in each assay and were in the range 2. Matrix effects ME were evaluated by the method by Matuszewski et al. Six replicates of urine from six different individuals were analyzed at two concentrations level 0. The substances tested were amisulpride MW Potential endogenous interferences were assessed by analyzing 10 urine specimens from different individuals.
No interferences were noted. Every year our laboratory receives several hundred urinary samples for the analysis of synthetic cannabinoids, including JWH and JWH The results from these analyses are stored in a large database. Five subjects in the database were of particular interest because there were numerous samples obtained during a limited period of time. All samples were sent from the same drug rehabilitation clinic. According to the staff at this clinic, they had over a short period of time experienced several episodes where suspected drug use among inpatients had been undetectable by regular urinary drug screening tests.
The suspected inpatients resided in a closed ward, and all had their belongings searched prior to unit entry. However, they all had access to a common living room, and were only intermittently monitored during night-time.
Moreover, inpatients were allowed to leave the ward for short periods of time, such as for jogging, and could after special application get permission to leave for longer periods, from hours to days.
Thus, drug use during hospitalization could not be ruled out, and the clinic staff decided to monitor the suspected inpatients with repeated urine samplings at least once or twice weekly, and had sent the specimens to our laboratory for additional testing. All urinary samples had been obtained under close surveillance.
The subjects included were three males and two females, with a mean age of Except for synthetic cannabinoids, no illicit drugs were detected Specimens were positive over a period of 20—43 mean In addition to the positive samples, three of the five subjects had negative specimens within the sequence of sampling. Subject B had negative samples after 31 and 37 days, subject C had a negative sample after 19 days and subject D had a negative sample after 8 days Table I.
Calculated urinary elimination half-lives were 4. There were no previous samples available from subjects A and B before the first positive sample was obtained. In contrast, in subjects C, D and E, samples had been obtained earlier during their same stay at the clinic; 1, 4 and 3 days before the index sample, respectively.
They were all negative Table II. Thus, in these subjects it was verified that the drug use had taken place over no more than one to a few days. Even when the duration of use prior to the index sampling was documented to be no more than 4 days, making tissue accumulation less likely, metabolites were detected for about 3 weeks. We consider it being a strength of this study that we could follow the excretion of JWH and JWH metabolites for a prolonged period of time with frequent urinary samplings.
The index sample from all subjects dated from the same day, except for two subjects who were not tested that day, but were tested 2 days later. This indicates that the drug ingestion took place at approximately the same time, and possibly inside the institution. Thus, it cannot be ruled out that additional intakes had taken place after the baseline samples were obtained, despite the ward surveillance.
However, the steadily falling slopes of the CN-concentrations Figure 2 clearly indicate residual urinary excretion and no new ingestion during the follow-up period. This study has some weaknesses, mostly caused by its naturalistic design. There were only five subjects included, and we had no information regarding dose and type of herbal mixture consumed.
Moreover, only one metabolite of each compound was analyzed. As various synthetic cannabinoids can produce overlapping metabolites, it might be necessary to analyze more than one metabolite of each compound to determine the intake of a specific substance with certainty 7. On the basis of this finding, the authors hypothesize that JWH could be demethylated to JWH in humans, although they cannot exclude that the subjects had had previous, non-reported intakes of JWH Interestingly, the metabolite pattern in urine was the same in these two subjects as in the third subject who consumed a mixture of JWH and JWH Unfortunately, no ratios between these metabolites are presented in that study.
The mean ratio was 1. This range is very close to the urinary ratios mean 1. We consider that these data indicate that those with the highest ratios had ingested JWH only, whereas those with a ratio closer to 1 most likely had ingested a mix. Thus, JWH most likely stems from another source. Although we cannot with certainty conclude whether the subjects in our study had ingested JWH only or a mixture of JWH and JWH, we therefore consider the latter being more likely.
We included AM—5-hydroxy in our method data not shown , but this metabolite was not detected in any of the samples. Consequently, there was no evidence that the blend consumed by the subjects in the present study contained AM An LOQ as low as 0.
For example, with a limit of 0. With an LOQ of 0. As this time frame was shorter than for subject C in our study who also may have had a single intake we suggest that the doses consumed by our subjects were higher than the one smoked by the drug-naive volunteer in the study by Jager et al. Jager et al. That time frame is shorter than the detection times found in our study. Due to the prolonged urinary excretion of metabolites of JWH and JWH, it could be a challenge to determine whether serial positive samples represent residual excretion from a previous intake, or a new intake.
To clarify this issue, calculations of CN-concentrations are essential. Consequently, the rate-limiting step in the elimination process of JWH and JWH could be redistribution from tissue depots back into circulation. Related to this assumption, it is worth noting that subject A and subject B who had the longest metabolite elimination times of the subjects included in our study, lacked negative samples taken prior to the first positive specimen in the series Table II.
Thus, it is not unlikely that these two subjects were chronic users, and that their slow metabolite elimination was caused by prior tissue accumulation during chronic use. Interestingly, they were also both women. As a consequence of the prolonged elimination phase, a positive sample after a negative sample does not necessarily represent a new intake.
In our study, subject B had two negative specimens on Day 31 and Day 37 during the course of sampling, whereas subject C and subject D had one negative specimen each on Day 19 and Day 8, respectively Table I. Thus, when the urine is as dilute as in these cases, a negative sample may well be falsely negative. Without calculated CN-concentrations of the analytes, the subjects risk being wrongly accused of new drug intake. For cannabis, various algorithms have been suggested to aid the interpretation of serial positive findings in urine after single and chronic use 2 , 24— Taking into consideration the similarities in pharmacokinetics, it seems reasonable that similar algorithms could be applied when differentiating new synthetic cannabinoid use from residual excretion.
However, far more background information, e. Even when the duration of use was no more than 4 days prior to the index sampling, making tissue accumulation less likely, metabolites were detected for about 3 weeks. Lakso H. Nilsson M. Journal of Analytical Toxicology , 32 , — Google Scholar.
Schwilke E. Gullberg R. Darwin W. Chiang C. Cadet J. Gorelick D. Addiction , , — Gunderson E. Abstract Referred to as 'spice', several new drugs, advertised as herbal blends, have appeared on the market in the last few years, in which the synthetic cannabinoids JWH and a C 8 homologue of CP 47, were identified as major active ingredients.
Publication types Research Support, Non-U. Gov't Validation Study. If for any reason our ability to provide services might change, we will communicate directly with our customers. User Name. Password Forgot your password? Synthetic Cannabinoids are chemicals that act as cannabinoid receptor agonists. Chemically they are not similar to cannabinoids but the term "Synthetic Cannabinoids" or "Cannabinomimetics" is widely used to refer to them as they're cannabinoid-like in their activity.
Little is known about the detailed pharmacology and toxicology of the synthetic cannabinoids and few formal human studies have been published. Synthetic Cannabinoids metabolize extensively in humans via oxidation and glucuronide conjugation. Following a single low dose, the hydroxylated synthetic cannabinoids and the carboxylated synthetic cannabinoids metabolites can be detected up to 72 hours in urine.
In case of chronic use, the detection window could be much longer. Very little parent drug excreted in human urine for most non-polar substances like JWH Presence of parent drug in saliva confirms ingestion; average detection window up to hours. There is considerable inter-and intra-batch variability in smoking mixtures, both in terms of substances present and their quantity. Thus, there is a higher potential for overdose than with cannabis.
Initially, JWH and JWH were the two most common synthetic cannabinoid chemicals found in a variety of herbal smoking blends. Reportedly offering a high 4 times stronger than marijuana, these compounds are commonly associated with herbal smoke and incense products sold under names such as K2, K3 Legal, Spice, Syn, Haze, Cloud Nine, Serenity and many others.
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