Detection of flubromazolam in patients with suspected non-medical drug use attending emergency departments in the United Kingdom

Figures & data

Figure 1. Chemical structure of flubromazolam and related benzodiazepines.

Table 1. Details of cases with analytically confirmed exposure to flubromazolam.

No.	Age/sex and presentation date/location	Reported drug use^a	Clinical features	Samples available	Substances detected
1	31 y female July 2020 SW England	FBZ Diazepam	GCS 13 Tachycardia (116/min) Hypotension (89/62 mmHg) Miosis	S	FBZ (67.9 ng/ml) Diazepam^c 4F-MDMB-BICA MDMB-4en-PINACA Carboxy-THC	Morphine^c Methadone^c Pregabalin Ketamine Cocaine^c
2	32 y male July 2020 SW England	Spice (smoked) Diazepam Ethanol	GCS 8 Miosis Agitation Confusion	S	FBZ (8.6 ng/ml) Diazepam^c 4F-MDMB-BICA 5F-EMB-PICA MDMB-4en-PINACA AB-FUBINACA	Carboxy THC Morphine Methadone^c Pregabalin Cocaine^c
3	40 y male July 2020 SW England	Unknown	GCS 13 Miosis Acidosis (pH 7.34)	S	FBZ (5.7 ng/ml) Flualprazolam Etizolam Diazepam 4F-MDMB-BICA 4F-MDMB-BINACA MDMB-4en-PINACA	Morphine Methadone^c Carboxy THC Pregabalin Cocaine^c
4	25 y male July 2020 London	LSD Ketamine Cannabis	GCS 14 Pyrexia (38.3 °C) Acidosis (pH 7.28, lactate 20 mmol/l) Agitation Confusion Hallucinations Elevated creatinine (154 mcmol/l)	B	FBZ (43.7 ng/ml) Hydroxyl-FBZ Flualprazolam Alprazolam	Diazepam^c Tramadol Ketamine
5	40 y male July 2020 SW England	Heroin (IV) Diazepam	GCS 9 Pyrexia (39.2 °C) Tachycardia (107/min) Agitation	S	FBZ (1.7 ng/ml) Hydroxyl-FBZ Clonazolam	Methadone^c Pregabalin
6	29 y female September 2020 SE England	Methadone Heroin (IV)	GCS 15 Acidosis (pH 7.34) Miosis Confusion	B	FBZ (6.2 ng/ml) Carboxy THC Morphine	Methadone^c Pregabalin Cocaine^c
7	30 y male October 2020 London	Alprazolam Diazepam Methamphetamine GBL	GCS 3 Acidosis (pH 6.79 pCO2 11.2 kPa, Base Excess 10.1 mmol/l) Vomiting Mydriasis Elevated potassium (5.9 mmol/l) ITU admission Intubation and ventilation (5 days)	B, U	FBZ (B,U) (28 ng/ml) (B) Hydroxyl-FBZ (B,U) Diazepam^c (B,U) Chlordiazepoxide (U) Alfentanil^d (U) Cocaine^c (B,U)	Tramadol (B,U) Codeine (B, U) MDMA (U) Amphetamine (B, U) Methamphetamine (B, U) Ketamine (B, U)
8	21 y male October 2020 SE England	Unknown Ketamine	GCS 15 Confusion	B	FBZ (480.5 ng/ml) Hydroxyl-FBZ Diazepam^c (B, U)
9	34 y male October 2020 NE England	Spice (smoked)	GCS 13 Seizure	S	FBZ [1] Hydroxyl-FBZ Chlordiazepoxide Diazepam^d	MDMB-4en-PINACA Morphine^c Methadone^c Gabapentin
10	20 y female December 2020 NE England	Diazepam Ketamine	GCS 5 Seizure Tachycardia (102/min) Hypotension (95 mmHg systolic) ITU admission Intubation and ventilation (1 day)	B	FBZ [1] Ketamine Cocaine^c
11	24 y male December 2020 Scotland	Alprazolam Cannabis Spice	GCS 13 Pyrexia (38.1 °C) Agitation Confusion Hallucinations Elevated CK 1824 IU/l	P, U	Hydroxyl-FBZ (P,U) Methamphetamine (P) Cocaine^c (P,U)	Etizolam^c (P) Diazepam^c (P,U) Carboxy-THC^c (P,U)
12	38 y male December 2020 SE England	Cocaine	GCS 8	B	FBZ [1] Codeine Gabapentin	Pregabalin Flualprazolam Diazepam^c
13	22 y male January 2021 Scotland	Heroin	GCS 15 Tachycardia (130) Acidosis (pH 7.19, pCO2 9.9) Pyrexia (38 °C)	P, U	FBZ^b (P,U) Hydroxyl-FBZ (P,U) Morphine^c (P,U) Codeine^c (P,U)	Cocaine^c (P,U) Modafinil^c (P,U) Diazepam^c (P,U)
14	42 y male January 2021 Scotland	Cannabis Diazepam	GCS 10 Hypothermia (33.5 °C) Confusion	P, U	FBZ^b (P,U) Hydroxyl-FBZ (P,U) Cocaine^c (P,U) Buprenorphine (P) Methadone^c (P,U)	Etizolam^c (P,U) Diazepam^c (P,U) MDMB-4en PINACA^c (P) Carboxy-THC (P)

B: whole blood; CK: creatine kinase; FBZ: flubromazolam; GBL: gamma butyrolactone; GCS: Glasgow Coma Score; IV: intravenous; ITU: intensive therapy unit; LSD: lysergic acid diethylamide; MDMA: 3,4-methylenedioxy-methamphetamine; P: plasma; S: serum; THC: tetrahydrocannabinol; U: urine.

^a Oral unless stated.

^b FBZ not quantified.

^c Including major metabolites.

^d Therapeutic administration in hospital.

Figure 2. Flubromazolam concentrations (whole blood, log scale) plotted against time after first sample in one participant (case 7) providing multiple blood samples. The equation for the line of best fit and the coefficient of determination (R²) are also provided.

Manchester KR, Lomas EC, Waters L, et al. The emergence of new psychoactive substance (NPS) benzodiazepines: a review. Drug Test Anal. 2018;10(2):392–393.

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