Concurrent Quantification of Emerging Chemicals of Health Concern in e-Cigarette Liquids by High-Performance Liquid Chromatography-Tandem Mass Spectrometry

Abstract

Emerging chemicals of concern (ECCs), including phthalate plasticizers, flame retardants, and phenolic compounds, are likely present in electronic nicotine delivery system (ENDS) replacement solutions (e-liquids) which are often packaged, stored in, and/or can contact with, plastic, glass, and metal materials. Developing and validating an efficient analytical method for concurrent quantification of ECCs in e-liquids are thus needed to inform evidence-based safety evaluation of ENDS products. In this study, we developed and validated a "dilute-and-shoot" method using high-performance liquid chromatography coupled with tandem mass spectrometry to simultaneously measure organophosphate flame retardants (OPFRs), phthalate plasticizers, and tetrabromobisphenol A (TBBPA) in e-liquids. We analyzed samples in positive electrospray ionization mode (ESI⁺) for OPFRs and phthalates and negative ESI^- for TBBPA. The method has a total runtime of 10 min. The optimized procedure was able to deliver broad dynamic linearity ranges with coefficients of determination (R ²) above 0.995, limits of detection ranging from 0.020 to 10 ng/mL, average accuracy within ±15%, and imprecision ≤ 15.0% for all analytes. To our knowledge, this is the first multianalysis method for measuring ECCs in e-liquid samples, and the validation results show that it is sensitive, accurate, precise, and efficient.

Figure 1

Examination of the effects of methanol fraction in the SPE washing solvent on the preparation recovery.

Figure 2

(a) Representative chromatograms for a standard sample with a spiked concentration of 16 ng/mL for TEP, DMP, TCEP, TPrP, and DEP. (b) Representative chromatograms of a standard sample with a spiked concentration of 16 ng/mL for TCPP, DCHP, TDCPP, TEHP, and TnBP. (c) Representative chromatograms of a standard sample with a spiked concentration of 16 ng/mL for TPhP, TDBPP, TBOEP, BBP, and DBP. (d) Representative chromatograms of a standard sample with a spiked concentration of 16 ng/mL for TCP, RDP, DAP, EHDPP, and DHP. (e) Representative chromatograms of a standard sample with a spiked concentration of 16 ng/mL for TBBPA.

Figure 3

Examination of the residual levels in blank samples analyzed prior to and following the samples with a concentration level of 250 ng/mL.