Hair as an Alternative Matrix in Bioanalysis

Barbosa, Joana; Faria, Juliana; Carvalho, Félix; Pedro, Madalena; Queirós, Odília; Moreira, Roxana; Dinis-Oliveira, Ricardo Jorge

doi:10.4155/bio.13.50

Cited by 78 publications

(51 citation statements)

References 128 publications

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“…Standard protocols are not available and several procedures to extract analytes from hair, such as extraction using organic solvents or aqueous buffers, digestion of the hair with NaOH or acid solutions and enzymatic digestion, have been combined with different separation and detection techniques, mainly GC-or LC-MS(/MS) [1,2]. Hair analysis is actively applied as an alternative matrix in different areas, such as clinical and forensic toxicology, abstinence monitoring for driving license regranting or child custody cases, workplace drug testing and doping control [3,4]. It provides some distinct advantages compared to traditional samples used in bioanalysis.…”

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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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: 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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“…In our study, all hair samples were cut from the posterior vertex region of the head. It is generally recognized that the proportion of hair in the telogen phase is the lowest and that hair growth rate shows less variability in this region [1,2]. Furthermore, all samples were collected by the same operator to minimize variation in the actual sampling site.…”

Section: Discussionmentioning

confidence: 99%

“…Owing to the ability to retrospectively determine drug use over a time window of several months (or even years), together with the long-term stability of many drugs in hair and the non-invasive sample collection, hair strands are collected as an alternative for, or in combination with, traditional blood or urine samples. On the other hand, important limitations associated with hair analysis are the lack of a clear-cut correlation between hair and plasma concentrations -the latter reflecting drug dose-for many substances and the risk of misinterpreting hair results due to external contamination [1,2].…”

Section: Introductionmentioning

confidence: 99%

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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“…Collection and analysis of hair has been implemented in various fields, including forensic toxicology, investigation of drug-facilitated crimes, workplace drug testing, doping control in sports, detection of perinatal drug exposure and abstinence monitoring in driving license regranting programs or child custody cases [45,46]. The most important feature of hair analysis is probably the possibility to retrospectively assess drug use.…”

Section: Hairmentioning

confidence: 99%

“…Furthermore, being a non-invasive sampling technique, collection of hair samples can be performed by non-specialized personnel, although some expertise is required to avoid variation in the amount of hair left on the scalp [47]. Hair strands are typically collected from the posterior vertex region of the head, as hair growth rate shows less variability there [45,46]. Although hair analysis provides distinct benefits compared to traditional bioanalytical matrices, it also holds important limitations, especially concerning the interpretation of hair results.…”

Section: Hairmentioning

confidence: 99%

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

2015

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Interindividual variability in the expression and function of drug metabolizing cytochrome P (CYP) 450 enzymes, determined by a combination of genetic, non-genetic and environmental parameters, is a major source of variable drug response. Phenotyping by administration of a selective enzyme substrate, followed by the determination of a specific phenotyping metric, is an appropriate approach to assess the in vivo activity of CYP450 enzymes, as it takes into account all influencing factors. A phenotyping protocol should be as simple and convenient as possible. Typically, phenotyping metrics are determined in traditional matrices, such as blood, plasma or urine. Several sampling strategies have been proposed as an alternative for these traditional sampling techniques.In this review, we provide a comprehensive overview of available methods using dried blood spots, hair, oral fluid, exhaled breath and sweat for in vivo CYP450 phenotyping. We discuss the relation between phenotyping metrics measured in these samples and those in conventional matrices, along with the advantages and limitations of the alternative sampling techniques. Reliable phenotyping procedures for several clinically relevant CYP450 enzymes, including CYP1A2, CYP2C19 and CYP2D6, are currently available for oral fluid, breath or dried blood spots, while additional studies are needed for other CYP450 isoforms, such as CYP3A4. The role of hair analysis for this purpose remains to be established. Being non-or minimally invasive, these sampling strategies provide convenient and patient-friendly alternatives for classical phenotyping procedures, which may contribute to the implementation of CYP450 phenotyping in clinical practice. 4 Key Points Phenotyping by administration of a selective probe drug, followed by determination of a specific phenotyping metric, allows to assess the in vivo enzyme activity of CYP450 enzymes, taking into account genetic, non-genetic and environmental influencing factors. In addition to classical sampling techniques, such as blood or urine collection, reliable phenotyping procedures for several clinically relevant CYP450 enzymes are currently available for oral fluid, breath and dried blood spots.

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Hair as an Alternative Matrix in Bioanalysis

Cited by 78 publications

References 128 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?

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

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