Is one hair lock really representative?

Dussy, Franz; Carson, N. B.; Hangartner, Sarah; Briellmann, Thomas

doi:10.1002/dta.1627

Cited by 16 publications

(17 citation statements)

References 4 publications

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“…Linearity was determined by constructing seven-point calibration lines (20,40,80,150,250,350, 500 pg/mg) for caffeine and paraxanthine on four consecutive days. An F-test at the 99 % confidence level was performed and residuals were plotted against nominal concentrations to evaluate homoscedasticity of the data [24].…”

Section: Validationmentioning

confidence: 99%

“…Given the generalized consumption of caffeine, intake of a test dose would no longer be required in the case of a phenotyping procedure involving hair analysis. Caffeine has been determined in hair using a variety of extraction media and analytical techniques, such as GC-MS, LC-UV, ion mobility MS, LC-QTOF-MS and LC-MS/MS [15][16][17][18][19][20], although only one published method was fully validated for caffeine [19]. To the best of our knowledge, our study is the first to provide an optimized and validated method for the combined determination of caffeine and its metabolite paraxanthine in hair.…”

Section: Introductionmentioning

confidence: 99%

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An optimized and validated SPE-LC–MS/MS method for the determination of caffeine and paraxanthine in hair

Kesel

Lambert

Stove

2015

Talanta

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Caffeine is the probe drug of choice to assess the phenotype of the drug metabolizing enzyme CYP1A2. Typically, molar concentration ratios of paraxanthine, caffeine's major metabolite, to its precursor are determined in plasma following administration of a caffeine test dose. The aim of this study was to develop and validate an LC-MS/MS method for the determination of caffeine and paraxanthine in hair. The different steps of a hair extraction procedure were thoroughly optimized. Following a three-step decontamination procedure, caffeine and paraxanthine were extracted from 20 mg of ground hair using a solution of protease type VIII in Tris buffer (pH 7.5). Resulting hair extracts were cleaned up on Strata-X ™ SPE cartridges.All samples were analyzed on a Waters Acquity UPLC ® system coupled to an AB SCIEX API 4000™ triple quadrupole mass spectrometer. The final method was fully validated based on international guidelines. Linear calibration lines for caffeine and paraxanthine ranged from 20 to 500 pg/mg. Precision (%RSD) and accuracy (%bias) were below 12 and 7 %, respectively. The isotopically labeled internal standards compensated for the ion suppression observed for both compounds. Relative matrix effects were below 15 %RSD. The recovery of the sample preparation procedure was high (> 85 %) and reproducible. Caffeine and paraxanthine were stable in hair for at least 644 days. The effect of the hair decontamination procedure was evaluated as well. Finally, the applicability of the developed procedure was demonstrated by determining caffeine and paraxanthine concentrations in hair samples of ten healthy volunteers. The optimized and validated method for determination of caffeine and paraxanthine in hair proved to be reliable and may serve to evaluate the potential of hair analysis for CYP1A2 phenotyping.

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Section: Validationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An optimized and validated SPE-LC–MS/MS method for the determination of caffeine and paraxanthine in hair

Kesel

Lambert

Stove

2015

Talanta

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“…Dussy et al determined caffeine concentrations in hair locks from 3 individuals collected at 10 different areas of the scalp. Coefficients of variation of measured caffeine concentrations ranged from 12.6 to 61.9 %, while a CV of 4.5 % was found for a homogenized control sample analyzed in six-fold [34]. However, it should be noted that the areas of sampling were widely distributed over the scalp, which could have contributed to the observed variability in measured concentrations as the proportions of hair in the anagen or telogen phase may vary in function of the location.…”

Section: Discussionmentioning

confidence: 92%

Paraxanthine/Caffeine Concentration Ratios in Hair: An Alternative for Plasma-Based Phenotyping of Cytochrome P450 1A2?

2015

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To refer to or to cite this work, please use the citation to the published version:De Kesel P., Lambert W. , Stove C. (2015). Paraxanthine/caffeine concentration ratios in hair: an alternative for plasma-based phenotyping of cytochrome P450 1A2? Clinical Pharmacokinetics, 54, 771-781. DOI 10.1007/s40262-015-0237-7 Paraxanthine/caffeine concentration ratios in hair: an alternative for plasma-based phenotyping of Abstract Background and ObjectiveAlthough metabolite-to-parent drug concentration ratios in hair have been suggested as a possible tool to study the metabolism of drugs in a non-invasive way, no studies are available that evaluate this in a systematic way. Cytochrome P450 (CYP) 1A2 is a drug metabolizing enzyme characterized by large inter-individual differences in its activity. The standard approach for CYP1A2 phenotyping is to determine the paraxanthine/caffeine ratio in plasma, at a fixed time point after intake of a dose of the CYP1A2 substrate caffeine. The aim of this study was to evaluate whether paraxanthine/caffeine ratios measured in hair samples reflect the plasma-based CYP1A2 phenotype. MethodsCaffeine and paraxanthine concentrations were measured in proximal 3-cm segments of hair samples from 60 healthy volunteers and resulting paraxanthine/caffeine ratios were correlated with CYP1A2 phenotyping indices in plasma. ResultsParaxanthine/caffeine ratios in hair ranged from 0.12 to 0.93 (median 0.41), corresponding ratios in plasma ranged from 0.09 to 0.95 (median 0.40). A statistically significant correlation was found between ratios in hair and plasma (r = 0.41, p = 0.0011). However, large deviations between ratios in both matrices were found in individual cases. Although the influence of several factors on paraxanthine/caffeine ratios and hair-plasma deviations was investigated, no evident factors explaining the observed variability could be identified. ConclusionThe variability between hair and plasma ratios complicates the interpretation of hair ratios on an individual basis and, therefore, compromises their practical usefulness as alternative CYP1A2 phenotyping metrics. Key Points For the first time, the usefulness of paraxanthine/caffeine molar concentrations ratios in hair for CYP1A2 phenotyping was evaluated by comparing hair ratios from 60 healthy volunteers with reference, plasma-based CYP1A2 phenotyping indices . Although ratios in hair and plasma showed a statistically significant correlation, large deviations were found in individual cases. Investigating the influence of several factors did not provide a clear explanation for the observed deviations, complicating the interpretation of hair ratios on an individual basis.

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“…However, the EtG concentrations in such hair samples may be different even if the same hair length is analyzed [54]. It is recommended to cut two locks: one for analysis and the second for a possible reanalysis in case of any doubt.…”

Section: Sampling Segmentation and Storagementioning

confidence: 99%

Alcohol Biomarkers in Hair

Pragst

2015

Hair Analysis in Clinical and Forensic Toxicology

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Is one hair lock really representative?

Cited by 16 publications

References 4 publications

An optimized and validated SPE-LC–MS/MS method for the determination of caffeine and paraxanthine in hair

An optimized and validated SPE-LC–MS/MS method for the determination of caffeine and paraxanthine in hair

Paraxanthine/Caffeine Concentration Ratios in Hair: An Alternative for Plasma-Based Phenotyping of Cytochrome P450 1A2?

Alcohol Biomarkers in Hair

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