Analysis of potential phenylacetone precursors (ethyl 3‐oxo‐2‐phenylbutyrate, methyl 3‐oxo‐4‐phenylbutyrate, and ethyl 3‐oxo‐4‐phenylbutyrate) by gas chromatography/mass spectrometry and their conversion to phenylacetone. Issue 3 (21st October 2021)

• Record Type: Journal Article
• Authors: Tsujikawa, Kenji; Okada, Yuki; Segawa, Hiroki; Kuwayama, Kenji; Yamamuro, Tadashi; Kanamori, Tatsuyuki; Iwata, Yuko T.
• Is Part Of: Drug testing and analysis. Volume 14:Issue 3(2022)
• Page Start: 439
• Page End: 449
• Publication Date: 2021-10-21
• Subjects: ethyl 3‐oxo‐2‐phenylbutyrate -- ethyl 3‐oxo‐4‐phenylbutyrate -- methoxime derivatization -- methyl 3‐oxo‐4‐phenylbutyrate -- phenylacetone; Drugs -- Analysis -- Periodicals; Drug testing -- Periodicals; Chemistry, Forensic -- Periodicals; 615.1901
• DOI: 10.1002/dta.3169
• Languages: English
• ISSNs: 1942-7603

Abstract

Abstract: Methyl 3‐oxo‐2‐phenylbutyrate (MAPA) is a recently circulating precursor of phenylacetone (P2P), a precursor of amphetamine and methamphetamine. MAPA has a hybrid chemical structure of acetoacetic acid ester and P2P. Acetoacetic acid ester is de‐esterified and decarboxylated to give the ketone by heating under acidic conditions; therefore, MAPA is presumed to be converted to P2P by such treatment. Considering that ethyl 3‐oxo‐2‐phenylbutyrate (EAPA), methyl 3‐oxo‐4‐phenylbutyrate (MGPA), and ethyl 3‐oxo‐4‐phenylbutyrate (EGPA) have the same chemical features as MAPA, these three compounds are potential P2P precursors. The authors examined the analysis of these compounds by gas chromatography–mass spectrometry (GC‐MS) and their conversion to P2P by heating under acidic and basic conditions. These compounds were remarkably decomposed into P2P during GC‐MS analysis regardless of the injection method and injector temperature. EAPA and EGPA also caused ester exchange to methyl ester by injection of methanol solution. P2P production and transesterification were almost prevented by methoxime derivatization. These compounds were converted to P2P by heating under acidic conditions. The reaction of MGPA and EGPA proceeded quicker than that of EAPA. The important by‐product associated with the reaction was phenylacetylcarbinol (formed from EAPA and MGPA), which will be converted to (pseudo)ephedrine, important methamphetamine impurities. By heating under basic conditions, MGPA and EGPA were converted to P2P but EAPA was mainly converted to phenylacetic acid. In the future, when these compounds are in circulation, our study will be useful for identifying and elucidating the synthetic method of P2P. Abstract : We evaluated GC‐MS analysis of three potential phenylacetone precursors (ethyl 3‐oxo‐2‐phenylbutyrate, methyl 3‐oxo‐4‐phenylbutyrate, and ethyl 3‐oxo‐4‐phenylbutyrate) and their conversion to phenylacetone by heating under acidic conditions. All compounds were decomposed to phenylacetone during GC‐MC analysis, and decomposition was almost prevented by methoximation. Heating under acidic condition converted them to phenylacetone.