Mouse Anti-AB-Pinaca Monoclonal antibody, clone H12410N

Whereas non-fluoropentylindole/indazole synthetic cannabinoids appear to be metabolized preferably at the pentyl chain though without clear preference for one specific position, their 5-fluoro analogs' major metabolites usually are 5-hydroxypentyl and pentanoic acid metabolites. We determined metabolic stability and metabolites of N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide (AB-PINACA) and 5-fluoro-AB-PINACA (5F-AB-PINACA), two new synthetic cannabinoids, and investigated if results were similar. In silico prediction was performed with MetaSite (Molecular Discovery). For metabolic stability, 1 mu mol/L of each compound was incubated with human liver microsomes for up to 1 h, and for metabolite profiling, 10 mu mol/L was incubated with pooled human hepatocytes for up to 3 h. Also, authentic urine specimens from AB-PINACA cases were hydrolyzed and extracted. All samples were analyzed by liquid chromatography high-resolution mass spectrometry on a TripleTOF 5600+ (AB SCIEX) with gradient elution (0.1% formic acid in water and acetonitrile). High-resolution full-scan mass spectrometry (MS) and information-dependent acquisition MS/MS data were analyzed with MetabolitePilot (AB SCIEX) using different data processing algorithms. Both drugs had intermediate clearance. We identified 23 AB-PINACA metabolites, generated by carboxamide hydrolysis, hydroxylation, ketone formation, carboxylation, epoxide formation with subsequent hydrolysis, or reaction combinations. We identified 18 5F-AB-PINACA metabolites, generated by the same biotransformations and oxidative defluorination producing 5-hydroxypentyl and pentanoic acid metabolites shared with AB-PINACA. Authentic urine specimens documented presence of these metabolites. AB-PINACA and 5F-AB-PINACA produced suggested metabolite patterns. AB-PINACA was predominantly hydrolyzed to AB-PINACA carboxylic acid, carbonyl-AB-PINACA, and hydroxypentyl AB-PINACA, likely in 4-position. The most intense 5F-AB-PINACA metabolites were AB-PINACA pentanoic acid and 5-hydroxypentyl-AB-PINACA.

The structures of two indazole-derived synthetic cannabimimetics, a methyl ester, MDMB-FUBINACA, and an amide, ADB-FUBINACA, differ only in the terminal groups on the side chains. Based upon liquid chromatography-quadrupole time-of-flight-mass spectrometry analysis of urine and blood samples collected from patients who were admitted to hospital with suspected drug intoxications and from postmortem forensic investigations, 38 metabolites were tentatively identified. Hydrolysis of the terminal groups (methyl ester and amide for MDMB-FUBINACA and ADB-FUBINACA, respectively) was found to be a common metabolic pathway for both compounds, leading to the formation of other common metabolites. Hydrolysed metabolites undergo subsequent monohydroxylation, dihydrodiol formation, fluorobenzyl loss and dehydrogenation. Most of the metabolites of MDMB-FUBINACA were products of ester hydrolysis. Metabolites formed by hydrolysis, additional monohydroxylation, dihydrodiol formation and fluorobenzyl loss were also detected in forms of glucuronides. Two unhydrolysed metabolites were identified as products of hydroxylation and fluorobenzyl loss with subsequent glucuronidation. In the case of ADB-FUBINACA, products of mono- and dihydroxylation, dihydrodiol formation, dihydrodiol formation combined with monohydroxylation, monohydroxylation combined with dehydrogenation and fluorobenzyl loss with monohydroxylation were identified. Monohydroxylated and dihydrodiol metabolites were also detected in the form of glucuronides. The most abundant metabolites were products of ester hydrolysis in free and glucuronidated forms (for MDMB-FUBINACA) and of dihydrodiol formation (for ADB-FUBINACA). These compounds are recommended for toxicological screening. To our knowledge, there are no reports dealing with the detection of metabolites of MBDB-FUBINACA and ADB-FUBINACA in authentic human urine specimens.