Fluorodeschloroketamine found as a street drug in drug seizures and drug driving cases in Hong Kong.

BACKGROUND: With the decline of the use of ketamine, one of the common drugs of abuse in Hong Kong, detection of ketamine-related analogues in local laboratories has been encountered. AIM: A brief account of the occurrence of fluorodeschloroketamine (FDCK) in forensic cases is reported through a retrospective study of all drug seizures and driving under the influence of drugs (DUID) cases since its first appearance. METHODS: Identification of FDCK in drug seizures was achieved through gas chromatography - mass spectrometry (GC-MS) and/or liquid chromatography - diode array detection (LC-DAD) methods while its quantification was performed using gas chromatography - flame ionization detection (GC-FID). For the analysis of blood samples in DUID cases, identification and quantification were performed using LC-MS/MS by monitoring the respective transitions of FDCK and fluorodeschloronorketamine (FDCNK) using ketamine-d4 and norketamine-d4 respectively as internal standards. RESULTS: Since its first submission in November 2018, a total of 74 drug seizure cases (151 items) and 6 drug driving cases were encountered till December 2019. Drug seizures found with FDCK were physically similar to those of ketamine seizures. The majority of items were detected with FDCK only (103 items, ∼67%) or as a mixture of FDCK with ketamine (42 items, ∼28%). The drug purity detected with either FDCK only or FDCK mixed with ketamine was high which was similar to those purity found in ketamine seizures. The blood drug concentrations of FDCK of the 6 drug driving cases were in the range of <0.002-1.1 µg/mL and other psychoactive drug(s)/metabolite(s) were also identified. Except for one case where the analysis of the metabolite, fluorodeschloronorketamine (FDCNK), was not conducted due to insufficient sample, the FDCK (FDCNK) concentrations in blood found in the 6 cases were <0.002 (0.005), 0.002 (0.002), 0.002 (0.003), 0.02 (0.035), 0.87 (0.44) and 1.1 (not determined) µg/mL. CONCLUSIONS: With the drug seizures found with FDCK resembled in physical appearance with ketamine seizures, users might likely misuse it as ketamine. Though complicated by other drugs found, it is speculated that the two cases with higher concentration of FDCK found in blood (1.1 and 0.87 µg/mL) might have contributed to the impairment observed.

Prevalence of drugs of abuse found in forensic testing of illicit drug seizures and urine samples from offenders/probationers in Hong Kong: A 3-year update.

The study investigates the prevalence of drugs of abuse detected from 2016 to 2018 through i) forensic drug testing of seizures from law enforcement agencies, and ii) common drugs of abuse for urinalysis of samples obtained from offenders/probationers under mandatory drug-use surveillance programmes. Under the selected drug testing groups, an average of 4677 cases/year (c.f. 5334 cases/year in 2011-2015) of illicit drug seizures and 19,501 samples/year (c.f. 28,438 samples/year in 2011-2015) for urinalysis, were examined from 2016 to 2018. The three most commonly encountered abused drugs in the period in both types of examinations were methamphetamine (MA), cocaine and heroin. The occurrence of ketamine, the most prevalent drug [1815 (34.0%) cases/year (for drug seizures), 2074 (7.3%) samples/year (for urinalysis)] in 2011-2015, had dropped significantly to 487 (10.4%) cases/year and 350 (1.8%) samples/year respectively. The drug positive rates for urinalysis in the selected population group (i.e., offenders/probationers requiring mandatory drug testing) increased steadily from 27.3% in 2016 to 30.8% in 2018 (an average of 29.0% vs. 22.1% in 2011-2015). The ratio of single drug use to more than one drug was about 4:1, showing predominant use of single drug. While MA was the most prevalent drug in the period, cases found with cocaine and cannabis increased steadily over the past 3 years. A rising trend was noted for cases identified with new psychoactive substances (NPS) in illicit drug seizures from an average of 87 cases/year in 2011-2015 to 211 cases/year in 2016-2018 although NPS cases still contributed to less than 5% of overall drug seizures. A total of 69 substances classified as NPS were encountered with 47 NPS newly encountered in 2016-2018 but 25 NPS found in 2011-2015 disappeared in this 3-year period. Cathinones, including both synthetic and plant-based, continued to be the major category of NPS cases (∼72%) in the region followed by synthetic cannabinoids, ketamine/PCP analogs and synthetic opioids.

The Emergence of Deschloro-N-ethyl-ketamine, a Ketamine Analog, in Drug Seizures and Drug Driving Cases in Hong Kong.

The study reports the detection of a newly emerged drug, deschloro-N-ethyl-ketamine (2-oxo-PCE), an analog of ketamine, through forensic drug and toxicological examinations of exhibits from drug seizure cases and blood samples taken from drivers of driving under the influence of drug (DUID) cases, respectively, in Hong Kong. The submission of 2-oxo-PCE in both types of cases was firstly encountered in October 2017. A total of 31 drug seizure cases (52 items) and 4 DUID cases were found positive with 2-oxo-PCE till October 2018. Drug seizures with 2-oxo-PCE found were all in physical form (mostly in powdery or crystalline solid), resembling those samples commonly found with ketamine but having much lower purity. Although the majority of the relevant items was found with 2-oxo-PCE as the only psychoactive substance (36 items, ~69%) or as a mixture with ketamine (10 items, ~19%), other psychoactive substances including methamphetamine, methylenedioxymethamphetamine and pentylone have also been encountered (6 items, 12%). For the four DUID cases, 2-oxo-PCE and its metabolite, deschloronorketamine, were detected in all blood samples. The 2-oxo-PCE concentrations in the four blood samples were in the range of 0.08-0.31 µg/mL, being higher than the concentrations of deschloronorketamine (in the range of 0.04-0.09 µg/mL) for each sample. The 2-oxo-PCE levels found were generally lower than the ketamine levels found in reported DUID cases. With items found with 2-oxo-PCE, which were physically indistinguishable from ketamine but having lower drug purity in seizures, the lower 2-oxo-PCE blood levels with more severe impairment signs observed for the drivers in DUID cases, it is not unreasonable to speculate that users might have taken it as ketamine without knowing of its real identity and hence was adversely affected by the more potent 2-oxo-PCE.

Prevalence of drugs of abuse found in testing of illicit drug seizures and urinalysis of selected population in Hong Kong.

The study investigates the prevalence of drugs of abuse detected from 2011 to 2015 through (i) forensic drug testing of illicit drug seizures from law enforcement agencies; and (ii) analysis of common drugs of abuse in urine samples obtained from offenders/probationers under mandatory drug-use surveillance programmes. Under the selected drug testing groups, there were an average of 5334 cases/year of illicit drug seizures examined and 28,438 samples/year requiring drugs of abuse analysis in urine, from 2011 to 2015. The drug positive rates for urinalysis in the selected population group (i.e., offenders/probationers requiring mandatory drug testing) were steady with an average of about 22%. The ratio of single drug use to more than one drug was about 4:1, showing predominant use of single drug. Ketamine, methamphetamine (MA) and heroin were the three most commonly encountered abused drugs through laboratory testing. During the period, identification of ketamine was shown to decline continuously in both illicit drug testing and urinalysis while there was substantial increase in detection of MA. A rising trend was noted for cases identified with new psychotropic substances (NPS) in illicit drug seizures although NPS cases contributed to a small proportion of overall drug seizure cases examined (<5%) in the study period. A total of 47 substances classified as NPS were encountered with cathinones, either synthetic or plant-based, contributed to the majority of NPS cases (˜77%) followed by synthetic cannabinoids and phenethylamines.

Forensic drug analysis of chloro-N,N-dimethylcathinone (CDC) and chloroethcathinone (CEC): Identification of 4-CDC and 4-CEC in drug seizures and differentiation from their ring-substituted positional isomers.

We report our findings for the determination of 4-chloro-N,N-dimethylcathinone (4-CDC), a newly encountered NPS in drug seizures examined in our laboratory, and its differentiation from 4-chloroethcathinone (4-CEC), one of the most common cathinones examined locally, and their respective regioisomers, namely 2-CDC and 3-CDC, as well as 2-CEC and 3-CEC in routine drug analysis. As CDCs and CECs have the same molecular mass of 211 with similar and non-characteristic spectra when analysed by gas chromatography-electron ionization-mass spectrometer (GC-EI-MS), it is imperative to establish methods easily amendable for forensic laboratories to differentiate these substances unambiguously. To confirm the identity of the solid, reference standards of all regioisomers of CDC (i.e., 2-CDC, 3-CDC and 4-CDC) and CEC (i.e., 2-CEC, 3-CEC and 4-CEC) were acquired and analysed using GC-EI-MS, liquid chromatography-diode array detector (LC-DAD) and Fourier Transform Infrared Spectrophotometer (FTIR) commonly used in routine forensic drug analysis. In addition, drug analysis with gas chromatography-chemical ionization-mass spectrometer (GC-CI-MS) using methane as the reagent gas operated in positive mode was also explored. It is found that using GC-EI-MS, all isomers of CDCs and CECs eluted with close but different retention times. However, the mass spectra between respective regioisomers were similar and difficult to distinguish. Using LC-DAD, the retention times of all studied cathinones were again different although there were partial overlap between 3-CDC and 4-CDC as well as between 3-CEC and 4-CEC but they all have distinguishable UV spectra. Apart from the detection of quasimolecular ion as the most prominent ion for each cathinone, GC-CI-MS is considered a superior technique to determine all six cathinones where each cathinone showed a unique fragmentation pattern for ease of identification. The analytical techniques have been applied for the examination of drug seizures where 4-CDC and 4-CEC were unambiguously identified either as a single component or mixed components in the seized materials. While FTIR is capable of providing confirmative structural information for the cathinones with each regioisomer exhibits a distinctive pattern but requiring high drug purity, LC-DAD and GC-CI-MS are demonstrated to be useful techniques that can readily differentiate structurally similar synthetic cathinones (even in mixtures) for routine forensic drug analysis.

A rapid and convenient LC/MS method for routine identification of methamphetamine/dimethylamphetamine and their metabolites in urine.

A rapid and sensitive LC/MS method was developed for the simultaneous analysis of N,N-dimethylamphetamine (DMA), N,N-dimethylamphetamine N-oxide (DMANO), methylamphetamine (MA) and amphetamine (A) in urine samples. Employing an Alltech C18 column for solid phase extraction followed by LC/MS analysis using an Alltech Platinum EPS C18 column with a mixture of ammonium formate (0.01 M, pH 3) and acetonitrile (77:23, v/v) as mobile phase at a flow rate of 0.2 mL/min, simultaneous identification and quantitation of A, MA, DMA and DMANO in urine can be achieved using a 5-min chromatographic run. The calibration ranges were 0.10-3.0 micro g/mL for DMANO, 0.05-3.0 micro g/mL for DMA and 0.05-5.0 micro g/mL for both MA and A. The intra-, inter-day precision and accuracy for all analytes, spiked at three different concentrations in quality control samples, were in the ranges of 1.7-8.6, 4.1-10.0, -11.6 to 12.9%, respectively. The newly developed method was applied to the analysis of urine samples obtained from 118 suspected MA/DMA abusers, with the presence of MA confirmed in their urine samples under the drug-use surveillance program. Of these 118 samples, 43 were found to contain DMANO and 11 with both DMANO and DMA.

The occurrence of alcohol/drugs by toxicological examination of selected drivers in Hong Kong.

The study is to investigate the extent of alcohol/drug(s) use among selected drivers, i.e. fatally injured drivers from traffic accidents (2006-2015), drink driving (2006-2015) and drug driving (2010-2015) cases, in Hong Kong. Between 2006 and 2015, specimens from a total of 223 fatally injured drivers were received for toxicological examination. Except for one driver, all other drivers with positive findings were male. Alcohol and/or drugs were detected in 60 (27%) cases where alcohol alone was detected in 40 cases (18%) while drugs with/without alcohol were detected in 20 cases (9%). A decreasing trend is observed for cases with blood/breath alcohol concentrations above the prescribed limits in both fatally injured drivers and drivers from drink driving cases in 2006-2015. Out of the 20 cases with positive findings in drugs, 8 of them were found with alcohol in which only one case found at level above the prescribed limit. The frequency of drugs encountered that are known to affect driving in blood is 31, representing an average of about 1.7 drugs per individual. Ketamine was the most frequently detected drug in fatally injured drivers. Sedatives/hypnotics (i.e. diazepam/nordiazepam, midazolam, 7-aminonimetazepam, 7-aminonitrazepam and zopiclone), morphine/monoacetylmorphine, cocaine/benzoylecgonine, methamphetamine, methadone and codeine were also detected. There has been a sharp increase in the submission of blood/urine specimens for toxicological analysis related to drug driving cases since 2010 with a total of 48 cases received in 2010-2011. With the introduction of legislative amendment of drug driving law since 2012, 154 cases were received in 2012-2015. The positive rates for drug driving cases examined were found to be 90% (43 out of 48 cases) in 2010-2011 and 89% (137 out of 154 cases) in 2012-2015. Drivers with single drug use were more frequently detected (40 cases in 2010-2011 and 82 cases in 2012-2015) than multiple drug use (3 cases in 2010-2011 and 55 cases in 2012-2015) but an increase in the use of more than one drug in driving population is noted. Ketamine was detected in the majority of cases (34 cases in 2010-2011 and 104 cases in 2012-2015). However, drug driving cases in recent years revealed that increase usages of methamphetamine, cocaine and zopiclone were observed. The mean, median and range of ketamine concentrations for 134 blood samples taken from drivers in drug driving cases were 0.34, 0.27, 0.01-1.8µg/mL respectively.

A high-throughput urinalysis of abused drugs based on a SPE-LC-MS/MS method coupled with an in-house developed post-analysis data treatment system.

A rapid urinalysis system based on SPE-LC-MS/MS with an in-house post-analysis data management system has been developed for the simultaneous identification and semi-quantitation of opiates (morphine, codeine), methadone, amphetamines (amphetamine, methylamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA)), 11-benzodiazepines or their metabolites and ketamine. The urine samples are subjected to automated solid phase extraction prior to analysis by LC-MS (Finnigan Surveyor LC connected to a Finnigan LCQ Advantage) fitted with an Alltech Rocket Platinum EPS C-18 column. With a single point calibration at the cut-off concentration for each analyte, simultaneous identification and semi-quantitation for the above mentioned drugs can be achieved in a 10 min run per urine sample. A computer macro-program package was developed to automatically retrieve appropriate data from the analytical data files, compare results with preset values (such as cut-off concentrations, MS matching scores) of each drug being analyzed and generate user-defined Excel reports to indicate all positive and negative results in batch-wise manner for ease of checking. The final analytical results are automatically copied into an Access database for report generation purposes. Through the use of automation in sample preparation, simultaneous identification and semi-quantitation by LC-MS/MS and a tailored made post-analysis data management system, this new urinalysis system significantly improves the quality of results, reduces the post-data treatment time, error due to data transfer and is suitable for high-throughput laboratory in batch-wise operation.

Chemical profiling of 3,4-methylenedioxymethamphetamine (MDMA) tablets seized in Hong Kong.

During 2000-2001, the Government Laboratory of Hong Kong received over 600,000 ecstasy tablets in more than 2,600 cases. Using GC-MS or FTIR, the major amphetamine-type stimulants were identified, and the samples were categorized into four groups containing: (1) 3,4-methylenedioxymethamphetamine (MDMA), (2) methamphetamine (MA), (3) 3,4-methylenedioxyamphetamine (MDA), or (4) amphetamine. Our study revealed that in Hong Kong MDMA tablets have made up 98 and 71% of the total ecstasy tablets examined in 2000 and 2001, respectively. Among the MDMA cases, 613 cases involving a total of 123,776 tablets in 2001 were randomly selected, and their active ingredients, minor ingredients, and/or impurities were studied using GC-MS and HPLC. Based on the chemical profiles, and irrespective of their different physical characteristics, tablets obtained in different seizures could be determined as to whether or not they could have come from a common origin. The impurities detected in the MDMA tablets also served as excellent chemical markers from which plausible synthetic route(s) of the MDMA were inferred. Our study revealed that 3,4-methylenedioxyphenyl-2-propanone (MDP2P), 3,4-methylenedioxyphenyl-2-propanol (MDP), 3,4-methylenedioxy-N-methylbenzylamine (MDB), piperonal and N-formyl-3,4-methylenedioxymethamphetamine (N-formyl-MDMA) were the most common impurities detected in MDMA tablets seized in Hong Kong. The finding of the phosphate salt of MDMA is intriguing. Based on a presumptive color test, spectroscopic data (FTIR/ESI-MS) and the percentage of MDMA content in a purified phosphate salt of MDMA, the ratio of the phosphate to MDMA was determined to be 1:1, suggesting that the compound is a dihydrogen phosphate salt [i.e. (HMDMA)H2PO4].

Enantiomeric separation of methamphetamine and related analogs by capillary zone electrophoresis: intelligence study in routine methamphetamine seizures.

A method for simultaneous enantiomeric separation of ephedrine, pseudoephedrine, and methamphetamine (MA) in a single run by simple capillary zone electrophoresis (CZE) with beta-cyclodextrin as a chiral selector is described. The effects of the buffer pH, phosphate concentration, beta-cyclodextrin concentration, voltage and temperature on the peak resolution were examined. Good enantiomeric resolution was attained for each analyte under our optimized conditions: 15 mM beta-cyclodextrin, 300 mM NaH2PO4 at pH 2.5 with an uncoated capillary (64.5 cm x 50 microm), applied potential at 20 kV and temperature at 30 degrees C. Ultraviolet (UV) detection at a fixed wavelength (200 nm) was employed using a diode array detector. Using phentermine as an internal standard, migration times for all analytes are reproducible within 0.16% for intra-day and 0.6% for inter-day runs. Application of this method to the analysis of confiscated drugs is discussed.

Roadside detection of impairment under the influence of ketamine--evaluation of ketamine impairment symptoms with reference to its concentration in oral fluid and urine.

Although there are many roadside testing devices available for the screening of abused drugs, none of them can be used for the detection of ketamine, a popular abused drug in Hong Kong. In connection to local drug driving legislation, effective roadside detection of ketamine in suspected drug-impaired drivers has to be established. According to the drug evaluation and classification program (DEC), ketamine is classified in the phencyclidine (PCP) category. However, no study has been performed regarding the signs and symptoms exhibited by users under the influence of ketamine. In a study to develop a protocol for effective roadside detection of drug-impaired drivers, 62 volunteers exiting from discos were assessed using field impairment tests (FIT) that included measurements of three vital signs (i.e. body temperature, pulse rate and blood pressure), three eye examinations [pupil size, lack of convergence (LOC) and horizontal gaze nystagmus (HGN)] and four divided attention tests (Romberg, one-leg stand, finger-to-nose and walk-and-turn tests). Subsequent laboratory analysis of oral fluid and urine samples from the participants revealed the presence of common abused drugs in both the urine and oral fluid samples of 55 subjects. The remaining 7 subjects with no drug in their oral fluid samples were used as drug-free subjects. In addition, 10 volunteers from the laboratory who were regarded as drug-free subjects were also assessed using the same FIT. Among the 62 volunteers, 39 of them were detected with ketamine in their oral fluid. Of these ketamine users, 21 of them (54%) with only ketamine found in their oral fluid samples while the rest (18 subjects) of them had other drugs (i.e. MA, MDMA, benzodiazepines and/or THC) in addition to ketamine. Of the 21 ketamine-only users, 15 of them (71%) were successfully identified by FIT. It was found that when salivary ketamine concentrations were greater than 300 ng/mL, signs of impairment became evident, with over 90% detection rate using the FIT. By comparing the FIT observations on the 21 ketamine-only users with the drug-free subjects, the typical signs and symptoms observable for subjects under the influence of ketamine included LOC, HGN, elevated pulse rate and in general, failing the divided attention tests, especially the walk-and-turn and one-leg stand.