Identification and quantitative analysis of impurities in tobacco-derived and synthetic nicotine: Is synthetic...

Synthetic nicotine (SN) is often advertised as safe and pure, in contrast to tobacco-derived nicotine (TDN). In this study, various impurities in both SN and TDN were identified through non-targeted chemical analysis using gas chromatography-mass spectrometry (GC-MS) followed by quantitative analysis using GC-MS/MS and high performance liquid chromatograph (HPLC)-MS/MS. Twenty-two impurities were detected in SN with a total concentration of 21,779 mg/kg; while twenty-eight impurities were detected in TDN with a total concentration of 10,967 mg/kg. Multiple alkaloid impurities detected in TDN were also found in SN. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its precursor, 4-(methylamino)-1 (3-pyridyl)-1-butanone, were detected in both TDN and SN. NNK was detected in samples with high precursor concentration in TDN or SN. This study is the first to detect NNK and its precursor in SN. N,N-Dimethylaniline, 1-methyl 2-pyrrolidinone and ethyl-2-pyrrolidinone are highly harmful by-products of nicotine synthesis and were detected at high levels in SN. In particular, 1-methyl-2-pyrrolidinone exceeded the US Pharmacopeia's residual solvent limit in two SN samples.