Rapid, sensitive, and reliable quantitation of nicotine and its main metabolites cotinine and trans-3′-hydroxycotinine by LC-MS/MS: Method development and validation for human plasma

Mallock, Nadja; Rabenstein, Andrea; Laux, Peter; Rüther, Tobias; Hutzler, Christoph; Parr, Maria Kristina; Luch, Andreas

doi:10.1016/j.jchromb.2021.122736

Cited by 9 publications

(5 citation statements)

References 39 publications

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“…To 990 µL plasma, 10 µL internal standard mix (500 ng/mL nicotine-d 3 , cotinine-d 3 , hydroxycotinine-d 3 in acetonitrile) at LMU in Munich, which occurred prior to storage at −80 °C and shipment to BfR in Berlin. Plasma levels of nicotine, cotinine, and trans-3′-hydroxycotinine (hydroxycotinine) were determined at BfR with a validated, previously published method using liquid chromatography–tandem mass spectrometry (LC-MS/MS) following protein precipitation [ 33 ]. A matrix-matched calibration was used for quantification.…”

Section: Methodsmentioning

confidence: 99%

Two Different Heated Tobacco Products vs. Cigarettes: Comparison of Nicotine Delivery and Subjective Effects in Experienced Users

Vukas,

Mallock-Ohnesorg,

Rüther

et al. 2023

Toxics

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Heated tobacco products (HTPs) produce aerosol using a different mechanism than tobacco cigarettes, leading to lower emissions of some harmful substances, but also of nicotine as reported by some independent studies. Lower nicotine delivery could lead to compensatory puffing when product use does not sufficiently satisfy cravings. Thus, this three-arm crossover study was conducted to characterize the potential of two different HTPs to deliver nicotine and satisfy cravings compared with conventional cigarettes in users who had already switched to HTPs. Fifteen active, non-exclusive HTP users consumed the study products according to a pre-directed puffing protocol. At predetermined time points, venous blood was sampled and the subjective effects of consumption were assessed. Nicotine delivery by both HTPs was comparable, but significantly lower than that by conventional cigarettes, suggesting a lower addictive potential. Cravings were reduced by all products, with no statistically significant differences between them, despite the different nicotine deliveries. This indicated that HTPs do not necessarily need high nicotine deliveries with high addictive potential, as are characteristic of tobacco cigarettes. These results were followed up on with an ad libitum use study.

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Section: Methodsmentioning

confidence: 99%

Two Different Heated Tobacco Products vs. Cigarettes: Comparison of Nicotine Delivery and Subjective Effects in Experienced Users

Vukas,

Mallock-Ohnesorg,

Rüther

et al. 2023

Toxics

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“…Samples were stored at LMU University Hospital in Munich at −80°C and shipped to BfR in Berlin on dry ice. A previously described validated method was used for the quantification of nicotine, cotinine, and trans-3′-hydroxycotinine (hydroxycotinine) from plasma using protein precipitation and liquid chromatography—tandem mass spectrometry (LC-MS/MS) with a matrix-matched calibration ( Mallock et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Small pouches, but high nicotine doses—nicotine delivery and acute effects after use of tobacco-free nicotine pouches

Mallock-Ohnesorg,

Rabenstein,

Stoll

et al. 2024

Front. Pharmacol.

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Tobacco-free nicotine pouches are new nicotine products for oral consumption. They can contain very high nicotine amounts that have not been addressed with clinical studies yet. Thus, nicotine delivery, effects on craving, and side effects were assessed using pouches with up to 30 mg nicotine. In this single-center, five-arm, crossover study, 15 regular cigarette smokers consumed tobacco-free nicotine pouches from different brands with 6, 20, and 30 mg for 20 min. Comparators were nicotine-free pouches and tobacco cigarettes. At baseline and predefined time points over a study period of 240 min, plasma nicotine concentrations, effects on cigarette craving, and side effects were assessed. Cardiovascular parameters including arterial stiffness were measured using a MobilOGraph. Consumption of 30 mg nicotine pouches has led to a higher nicotine uptake compared with the cigarette (Cmax: 29.4 vs 15.2 ng/mL; AUC: 45.7 vs 22.1 ng/mL × h). Nicotine uptake in the acute phase was rapid during use of the 30 mg pouch and cigarette. Extraction rate of nicotine differed between pouches. Use of all products has reduced acute cigarette craving, even the nicotine-free pouch. During consumption of the cigarette and the pouches with 20 and 30 mg, heart rate increased about 27, 12, and 25 bpm, respectively. Parameters for arterial stiffness were elevated and all pouches have induced mouth irritations. The pouches with 30 mg nicotine had overall the strongest side effects and may induce addiction. As craving was also reduced by products with less nicotine, it is questionable whether such high nicotine contents should be allowed on the market. A limit of nicotine content is warranted. The nicotine release rate varies across products and needs to be known to estimate the nicotine delivery.

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“…A matrix-matched calibration was used for quantification. Details of the validated analytical method were previously published [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

“…A matrix-matched calibration was used for quantification. Details of the validated analytical method were previously published [25]. The German version of the QSU (Questionnaire on Smoking Urges) was used to measure reduction in product use urges at baseline and after completion of the session [30].…”

Section: Blood Sampling and Determination Of Nictoine Cotinine And Hy...mentioning

confidence: 99%

“…At predetermined time points, blood was sampled to determine plasma nicotine concentrations. Nicotine concentrations were measured using a previously published method for quantifying nicotine and its major metabolites, cotinine and trans-3′-hydroxycotinine, by LC-MS/MS in human plasma [ 25 ]. Subjective effects of product use were inquired using questionnaires.…”

Section: Introductionmentioning

confidence: 99%

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Usage Pattern and Nicotine Delivery during Ad Libitum Consumption of Pod E-Cigarettes and Heated Tobacco Products

Rabenstein

Rahofer

Vukas

et al. 2023

Toxics

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Many different nicotine delivery products, such as e-cigarettes (e-cigs) or heated tobacco products (HTPs), are available on the market. To better understand these products, it is crucial to learn how consumers use them and how much nicotine they deliver. Therefore, a pod e-cig, an HTP, and a conventional cigarette (CC) were each used by 15 experienced users of the respective product category for 90 min without special use instructions (“ad libitum”). Sessions were video recorded to analyze usage patterns and puff topography. At defined time points, blood was sampled to determine nicotine concentrations, and subjective effects were inquired about using questionnaires. During the study period, the CC and HTP groups averaged the same number of consumption units (both 4.2 units). In the pod e-cig group, the highest number of puffs was taken (pod e-cig 71.9; HTP: 52.2; CC: 42.3 puffs) with the most extended mean puff duration (pod e-cig: 2.8 s; HTP: 1.9 s; CC: 1.8 s). Pod e-cigs were predominantly used with single puffs or in short clusters of 2–5 puffs. The maximum plasma nicotine concentration was highest for CCs, followed by HTPs, and then pod e-cigs with 24.0, 17.7, and 8.0 ng/mL, respectively. Craving was reduced by all products. The results suggest that the high nicotine delivery known for tobacco-containing products (CCs and HTPs) may not be needed for non-tobacco-containing products (pod e-cigs) to satisfy cravings in experienced users.

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Rapid, sensitive, and reliable quantitation of nicotine and its main metabolites cotinine and trans-3′-hydroxycotinine by LC-MS/MS: Method development and validation for human plasma

Cited by 9 publications

References 39 publications

Two Different Heated Tobacco Products vs. Cigarettes: Comparison of Nicotine Delivery and Subjective Effects in Experienced Users

Two Different Heated Tobacco Products vs. Cigarettes: Comparison of Nicotine Delivery and Subjective Effects in Experienced Users

Small pouches, but high nicotine doses—nicotine delivery and acute effects after use of tobacco-free nicotine pouches

Usage Pattern and Nicotine Delivery during Ad Libitum Consumption of Pod E-Cigarettes and Heated Tobacco Products

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