Method Validation Approaches for Analysis of Constituents in ENDS

Reilly, Steve; Cheng, Tianrong; DuMond, Jenna

doi:10.18001/trs.6.4.3

Cited by 4 publications

(5 citation statements)

References 150 publications

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“…Testing was performed at two facilities: Durham, NC and Richmond, VA, which held ISO 17025:2017 and ISO 17025:2005 accreditation standards, respectively, at the time of testing. All analytical methods were validated to ensure reliability and accuracy and assessed for specificity, linearity, accuracy, precision, range, repeatability, or robustness. PG, VG, and nicotine were measured in the aerosols by gas chromatography–flame ionization detection (GC–FID) collected from the cascade impactor foils using method ENT185 or from CFPs using method AM-201 (see Supporting Information for full method details used in this study).…”

Section: Methodssupporting

confidence: 87%

Physical and Chemical Characterization of Aerosols Produced from Experimentally Designed Nicotine Salt-Based E-Liquids

Harris

2024

Chem. Res. Toxicol.

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Nicotine salt-based e-liquids deliver nicotine more rapidly and efficiently to electronic nicotine delivery system (ENDS) users than freebase nicotine formulations. Nicotine salt-based products represent a substantial majority of the United States ENDS market. Despite the popularity of nicotine salt formulations, the chemical and physical characteristics of aerosols produced by nicotine salt e-liquids are still not well understood. To address this, this study reports the harmful and potentially harmful constituents (HPHCs) and particle sizes of aerosols produced by laboratory-made freebase nicotine and nicotine salt e-liquids. The nicotine salt e-liquids were formulated with benzoic acid, citric acid, lactic acid, malic acid, or oxalic acid. The nicotine salt aerosols had different HPHC profiles than the freebase nicotine aerosols, indicating that the carboxylic acids were not innocent bystanders. The polycarboxylic acid e-liquids containing citric acid, malic acid, or oxalic acid produced higher acrolein yields than the monocarboxylic acid e-liquids containing benzoic acid or lactic acid. Across most PG:VG ratios, nicotine benzoate or nicotine lactate aerosols contained the highest nicotine quantities (in %) and the highest nicotine yields (per milligram of aerosol). Additionally, the nicotine benzoate and nicotine lactate e-liquids produced the highest carboxylic acid yields under all tested conditions. The lower acid yields of the citric, malic, and oxalic acid formulations are potentially due to a combination of factors such as lower transfer efficiencies, lower thermostabilities, and greater susceptibility to side reactions because of their additional carboxyl groups serving as new sites for reactivity. For all nicotine formulations, the particle size characteristics were primarily controlled by the e-liquid solvent ratios, and there were no clear trends between nicotine salt and freebase nicotine aerosols that indicated nicotine protonation affected particle size. The carboxylic acids impacted aerosol output, nicotine delivery, and HPHC yields in distinct ways such that interchanging them in ENDS can potentially cause downstream effects.

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Section: Methodssupporting

confidence: 87%

Physical and Chemical Characterization of Aerosols Produced from Experimentally Designed Nicotine Salt-Based E-Liquids

Harris

2024

Chem. Res. Toxicol.

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“…At the beginning of the clinical chemistry examination, partial validation was carried out, namely, sensitivity (quantification limits), linearity, repeatability, and reproducibility (referring to [ 12 ]), then the ALT, AST, creatinine, and BUN examinations were carried out below. The 100 μ L serum samples were added to 1 mL of kit reagent for ALT and AST (Sigma-Aldrich, Corp., US, catalog numbers MAK052-1KT and MAK055-1KT), shaken well for 5 minutes, and incubated for 2 minutes at 37°C.…”

Section: Methodsmentioning

confidence: 99%

In Vivo Analysis of Extract of Leaves of Mistletoe as a Benalu Duku: Clinical Chemical Value Associated with Histopathology, Liver, Kidneys, and Lethal Dose Determinate

Lazuardi

Chien

et al. 2022

Veterinary Medicine International

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The active compounds from the leaves of Dendrophthoe pentandra L. Miq., also known as, Benalu Duku (in Indonesia), are known to contain progesterone-like compounds (PLCs). This study aims to determine the effect of giving a single dose of PLCs on liver and kidney function in rats and the dose limit that causes the death of experimental animals. The PLCs were analyzed for chemical and physical characterization and compared to a pure standard of progesterone using HPLC, IR spectrometry, thermogravimetry, and NMR. The research was carried out in two sections. In section one, thirty-five healthy adult male rats were divided into six experimental groups and a control group of five rats each. The groups received, respectively, 50 to 75 mg/kg of PLCs (i.p.). The control group was given a 0.5 mL Aqua Pro injection. Alanine aminotransferase, aspartate aminotransferase, creatinine, and blood urea nitrogen were assessed using the clinical chemistry of blood serum analysis. Cell disruptions were analyzed to determine the degeneration effects of PLCs on the liver and kidney in the experimental and control groups. In section two, thirty healthy adult male rats were divided into 6 groups, each group of 5 rats, and injected with PLCs at a dose of 0.9–2.1 g/kg BW, followed by a lethal dose test. The control groups were available for 5 individual rats at 0 g/kg BW of PLCs. Our findings indicated that PLCs have a similarity chemical and physical characterized each other compounds, then the following administration of 50 to 75 mg/kg of PLCs did not affect the parameters of clinical chemistry. Histopathology analysis of the liver and kidney revealed normal subcellular levels in the experimental group, with the nonlethal dose at 0.9 g/kg BW.

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“…Figure 1 is a heatmap that displays the percentage of brands for which HPHCs were quantifiable in this study. For the six HPHCs (anabasine, acrylamide, catechol, cobalt, nornicotine, o-toluidine) quantifiable in both e-liquids and aerosols, the comparison analyses conducted across matrices for 35 aerosols, generated from degradation or heat formation, leached from product components, contaminated from product use or testing, or resulted from a combination of multiple sources. For example, all six HPHCs are quantifiable in both e-liquids and aerosols with overlapping products between the two matrices for anabasine, catechol, nornicotine, and o-toluidine but little to no overlapping products for acrylamide and cobalt.…”

Section: T H Imentioning

confidence: 99%

“…Two JUUL products (i.e., Fruit, Creme) were taken off the U.S. market during our product procurement; as a result, the acquired quantity was sufficient for testing in e-liquids only. To mitigate the impact of this occurrence, we used two JUUL products -Caffeic Acid -Acrolein 11,25,[34][35][36][37][38][39][40]43,44,46,48 -Benzene 29,30,35 -Indeno [1,2,3-cd] pyrene (IcdP) 29 -Carbon Monoxide (CO) 7,32,33 -Crotonaldehyde 35,38,42,47,48 -Styrene (i.e., CA Fruit, CA Vanilla) from the Canadian market for aerosol HPHC testing. As it is unknown whether the products of the same flavor from the U.S. and Canadian markets were identical, data from these products were not used to evaluate the e-liquid-to-aerosol transfer.…”

Section: ■ Introductionmentioning

confidence: 99%

Harmful and Potentially Harmful Constituents in E-Liquids and Aerosols from Electronic Nicotine Delivery Systems (ENDS)

Reilly,

Cheng,

Feng

et al. 2024

Chem. Res. Toxicol.

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In 2012, the U.S. Food & Drug Administration (FDA) published an established list of 93 harmful and potentially harmful constituents (HPHCs) targeting four tobacco product types (cigarettes, cigarette tobacco, roll-your-own tobacco, smokeless tobacco). In 2016, the FDA finalized the deeming rule to regulate electronic nicotine delivery systems (ENDS). However, knowledge gaps exist regarding whether certain HPHCs are present in ENDS e-liquids and aerosols. We identified and addressed these gaps by conducting literature searches and then experimentally quantifying HPHCs in the e-liquid and aerosol of 37 ENDS brands based on gaps in the literature. The literature searches identified 66 e-liquid HPHCs and 68 aerosol HPHCs that have limited to no information regarding the quantifiability of these constituents. A contracted ISO 17025 accredited laboratory performed the HPHC quantifications. The availability of validated analytical methods in the contracted laboratory determined the HPHCs included in the study scope (63/66 for e-liquids, 64/68 for aerosols). Combining the results from the quantifications and literature searches, 36 (39%) and 34 (37%) HPHCs were found quantifiable (≥limit of quantification [LOQ]) in ENDS e-liquids and aerosols, respectively, with 25 HPHCs being quantifiable in both matrices. Quantifiability results imply potential HPHC transfers between matrices, leaching from components, or formations from aerosol generation. The study results can inform the scientific basis for manufacturers and regulators regarding regulatory requirements for HPHC reporting. The HPHC quantities can also inform evaluations of the public health impact of ENDS and public communications regarding ENDS health risks.

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Method Validation Approaches for Analysis of Constituents in ENDS

Cited by 4 publications

References 150 publications

Physical and Chemical Characterization of Aerosols Produced from Experimentally Designed Nicotine Salt-Based E-Liquids

Physical and Chemical Characterization of Aerosols Produced from Experimentally Designed Nicotine Salt-Based E-Liquids

In Vivo Analysis of Extract of Leaves of Mistletoe as a Benalu Duku: Clinical Chemical Value Associated with Histopathology, Liver, Kidneys, and Lethal Dose Determinate

Harmful and Potentially Harmful Constituents in E-Liquids and Aerosols from Electronic Nicotine Delivery Systems (ENDS)

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