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The SDC urine samples were positive for 9 different benzodiazepine analytes. Table 53 displays the number of positive urine samples for the benzodiazepine drugs tested. All other samples were negative for the benzodiazepines specified in Table 51. Concentrations are not reported, as this was a qualitative study.

Due to the complex nature of the benzodiazepine class of drugs, care must be taken when interpreting benzodiazepines detected in urine. Benzodiazepines often metabolise, or break down, to other active benzodiazepine drugs, e.g. diclazepam forms delorazepam, lorazepam and lormetazepam in the body. In addition to being active metabolites, these substances are drugs in their own right, and some can be formed from more than one parent drug e.g. delorazepam is a metabolite of both diclazepam and cloxazolam (not licensed for use in the UK, prescribed in Italy). (Manchester et al., 2018; Moosmann, Bisel and Auwärter, 2014)

Diazepam is the most prescribed benzodiazepine worldwide and metabolises to three other active drugs, desmethyldiazepam, oxazepam and temazepam. Desmethyldiazepam is also a metabolite of six other benzodiazepine drugs. Diazepam and its metabolites were the most detected benzodiazepines in this study.

Table 53: SDC number of urine samples positive for benzodiazepines Analyte No. of Positives

Diazepam 15 Desmethyldiazepam 34 Temazepam 35 Oxazepam 40 Delorazepam 2 Lorazepam 5 Lormetazepam 2 Etizolam 1 Metizolam 1

The results showed 2 positives for delorazepam indicating diclazepam use, (Moosmann, Bisel and Auwärter, 2014) DC 41 and DC 72, see Table 54. In addition sample DC 41 was positive for a further 2 diclazepam metabolites

134 (lorazepam and lormetazepam). Lorazepam and lormetazepam are clinical drugs in Scotland however not commonly prescribed, especially compared to benzodiazepines such as diazepam, see section 1.3 in chapter 1. The combination of the drugs together also adds weight that they are the product of diclazepam metabolism rather than lorazepam and lormetazepam consumption. Sample DC 41 was collected from a 30-year-old male, his questionnaire does not mention any benzodiazepines; it states he had only taken methadone in the week prior to sample collection. It is reasonable to conclude that DC 72 and DC 41 have used diclazepam as they are positive for more than one of its metabolites. Diclazepam metabolism is discussed in section 1 .7 of chapter 1. The questionnaires for DC 41, DC 72 and DC 49 state they are all male and they had only taken methadone in the week prior to sample collection. DC 41 and DC 49 are positive for diazepam metabolites but not diazepam itself, which is not unusual in urine samples. (Temte

et al., 2018) DC 64 and DC 65 are positive for lorazepam only, which may be from

the use of prescribed lorazepam, although this was not stated, or the use of diclazepam. DC 64 is a 36-year-old male who stated he had taken diazepam from a dealer as well as methadone and cannabis in the week prior to his sample collection. DC 65 is a 65-year-old male who states he had taken heroin and methadone in the week prior to his sample collection.

Table 54: NHS GDDC urine samples positive for diclazepam metabolites Sample number Age Sex Drug mentioned

on questionnaire Toxicology findings DC 41 30 M Methadone Delorazepam Lorazepam Lormetazepam Oxazepam Temazepam Desmethyldiazepam DC 49 34 M Methadone Lorazepam Lormetazepam Oxazepam Temazepam Desmethyldiazepam DC 72 51 M Methadone Delorazepam Lorazepam Oxazepam Temazepam Desmethyldiazepam Diazepam

Sample DC 53 was positive for both etizolam and metizolam, see section 5.5.1.3 for an investigation into the metizolam positive samples.

Sample DC 53 was also positive for diazepam and all three metabolites. Sample DC 53 was collected from a 36-year-old male who stated in his questionnaire that he had taken ‗benzodiazepines‘ in the form of 5 x 5mg street diazepam he had

135 purchased from a dealer. He states he took these the day before attending the Drug Court to provide his urine sample. DC 53 was the only sample positive for etizolam. This is unusual as etizolam has been shown to be a very popular drug in Scotland however no metabolites for etizolam were in the method and this will reduce detection. The half-life of etizolam is 3 to 7 hours (Høiseth, Tuv and Karinen, 2016) and is much shorter than diazepam and diclazepam (20-50 and 42 hours respectively) so therefore etizolam has a shorter window of detection compared to diazepam and diclazepam.

It is reasonable to speculate that all of the positive results for oxazepam, temazepam and desmethyldiazepam came from diazepam use as these are the major diazepam urinary metabolites and as discussed in 1.3 of chapter 1 diazepam is much more available than oxazepam. (Temte et al., 2018) The 15 positives for diazepam are also positive for all three diazepam metabolites.

In total there were 40 (55%) samples positive for benzodiazepines, all 40 were positive for more than one analyte tested. This is higher than the reported use on the questionnaires. As the result of the dip stick tests were never reported to the author, it is not possible to compare the results of this analysis to the dip stick results. This study shows that benzodiazepine use is common in this population and it is possible that individuals may be using designer benzodiazepines either in an attempt to evade detection by the immunoassay tests used in mandatory drug testing or inadvertently due to illicitly made ―valium‖ tablets. (Kirby, 2016) The ability to evade detection is a concern for the healthcare workers in these settings however in this study the samples in which designer benzodiazepines detected were all positive for diazepam and therefore would test positive by immunoassay leaving this question not fully answered. The study is also voluntary and thereby users may have not agreed to take part if they had recently used designer benzodiazepines. The use of benzodiazepines is common amongst opioid users as they can be used to enhance the high or to self-medicate during withdrawals or insomnia. (Jones, Mogali and Comer, 2012)