Drugs In Hair Research Articles

A validated liquid chromatography/tandem mass spectrometry method for the analysis of efavirenz in 0.2 mg hair samples from human immunodeficiency virus infected patients.

Drug levels in hair provide a longer window of detection, compared to plasma drug levels, and therefore hair analysis has the advantage of assessing adherence over a longer period of time. No methods for the analysis of antiretroviral drugs in hair currently exist in South Africa, and worldwide there is only one validated method for the determination of efavirenz in hair that has been published. Efavirenz was extracted from 0.2mg of hair through a simultaneous pulverization and extraction step. Separation was achieved on an Agilent Poroshell C18 column using an isocratic elution with a total run time of 3min. A triple quadrupole mass spectrometer set to electrospray ionization in positive multiple reaction monitoring mode was used for detection. The method was validated over the concentration range 0.625-40ng/mg. Using ten times less hair than in a previously published method, the lower limit of quantitation was validated at 0.625ng/mg. The interday and intraday assay precision, expressed as the percentage coefficient of variation (CV), for spiked calibration standards and quality control samples was lower than 7% and accuracy ranged from 97 to 110%. For quality controls prepared from authentic hair the CV was less than 12%. The extraction efficiency for authentic quality control samples was determined to be 83% after repeated extractions of the same samples. This paper reports the first quantitative method for the determination of efavirenz in hair to be developed in South Africa. The validated method allowed for the successful monitoring of efavirenz in hair collected from HIV-infected patients as part of a clinical study.

Assessment of Pregabalin Use by Hair Testing

ABSTRACTBackground: The detection and analysis of drugs in hair has progressively emerged as a consequence of the enhanced sensitivity of analytical techniques used in forensic toxicology; a greater advantage in using this matrix respect to classical ones (i.e., urine and blood) is an easier and noninvasive sample collection, even when the careful supervision of law-enforcement officers is required to avoid the risk that the sample may be adulterated or replaced. Moreover, according to the length of the hair, the history of drug exposure can be retrospectively monitored from few weeks up to months or years since sample collection. Objective: Given the potential negative effects of pregabalin, an antiepileptic and analgesic drug with a high risk of misuse and abuse, the laboratory was asked to test for the drug in hair. Method: A new ultrahigh-performance liquid chromatography coupled to tandem mass spectrometry was developed. The method involves incubation of 25 mg of cut hair in acetonitrile for 2 h in an ultrasonic bath and separation on an Acquity HSS C18 column (150 × 2.1 mm × 1.8 µm) maintained at 50°C in a thermostatically controlled oven. A gradient elution was performed. Results: The method was fully validated according to international standards. The limit of quantitation of the test was 10 pg/mg. Five authentic cases of pregabalin in hair segments were tested using the method and the results were in the range 17–1487 pg/mg. Conclusion: This new method was found suitable to monitor both patients under pregabalin therapy and dependent subjects.

Simultaneous determination of antiretroviral drugs in human hair with liquid chromatography-electrospray ionization-tandem mass spectrometry

The determination of the concentrations of antiretroviral drugs in hair is believed to be an important means for the assessment of the long-term adherence to highly active antiretroviral therapy. At present, the combination of tenofovir, lamivudine and nevirapine is widely used in China. However, there was no research reporting simultaneous determination of the three drugs in hair. The present study aimed to develop a sensitive method for simultaneous determination of the three drugs in 2-mg and 10-mg natural hair (Method 1 and Method 2). Hair samples were incubated in methanol at 37 °C for 16 h after being rinsed with methanol twice. The analysis was performed on high performance liquid chromatography tandem mass spectrometry with electronic spray ionization in positive mode and multiple reactions monitoring. Method 1 and Method 2 showed the limits of detection at 160 and 30 pg/mg for tenofovir, at 5 and 6 pg/mg for lamivudine and at 15 and 3 pg/mg for nevirapine. The two methods showed good linearity with the square of correlation coefficient >0.99 at the ranges of 416–5000 and 77–5000 pg/mg for tenofovir, 12–5000 and 15–5000 pg/mg for lamivudine and 39–50,000 and 6–50,000 pg/mg for nevirapine. They gave intra-day and inter-day coefficient of variation <15% and the recoveries ranging from 80.6 to 122.3% and from 83.1 to 114.4%. Method 2 showed LOD and LOQ better than Method 1 for tenofovir and nevirapine and matched Method 1 for lamivudine, but there was high consistency between them in the determination of the three drugs in hair. The population analysis with Method 2 revealed that the concentrations in hair were decreased with the distance of hair segment away from the scalp for the three antiretroviral drugs.

Does Performing Preplacement Workplace Hair Drug Testing Influence US Department of Transportation Random and Postaccident Urine Drug Test Positivity Rates?

Does performing pre-employment hair drug testing subsequently affect the prevalence of positive random and postaccident urine drug tests? This cross-sectional study was designed to evaluate the prevalence of positive postaccident and random workplace urine drug tests for companies that perform pre-employment hair and urine drug testing to companies that only perform pre-employment urine drug testing. Fisher exact test of independence indicated no significant difference between pre-employment hair drug testing and overall US Department of Transportation random and postaccident urine drug test positivity rates. The analysis failed to reject the null hypothesis, suggesting that pre-employment hair drug testing had no effect upon random and postaccident urine drug test positivity rates.

Hair analysis when external contamination is in question: A review of practical approach for the interpretation of results

Despite having been extensively discussed over the last decade, the differentiation between systemic exposure and external contamination still continues to be one of the limitations of hair testing for drugs. For this reason, we consider it worthwhile to re-state some basic principles in this short review. Various studies investigating a diversity of wash protocols, most using artificially contaminated hair with cocaine, have been valuable in evaluating wash efficacy and in understanding the incorporation of drugs in hair. However, assessments of wash efficacy made with real hair samples, as opposed to artificially contaminated samples, provide a different perspective, and demonstrate how rarely external contamination affects the interpretation of results. Data from a large number of hair samples from crack cocaine users, confirmed the usefulness of our protocol to remove most of the externally deposited cocaine. The data showed that hair levels of cocaine and benzoylecgonine in crack cocaine users were overall high with ratio of benzoylecgonine to cocaine in all samples above 0.1. The wash residue concentrations of cocaine ranged from not detected to 21ng/mg with a median of 0.5ng/mg. Cocaine was detected in the wash residue in 105 out of 138 samples. The wash to hair cocaine ratio ranged from not detected to 0.36 with a median of 0.02. The wash to hair cocaine ratios were below 0.07 in 133 cases. The five cases that produced wash to hair ratios above 0.1, one sample was at 0.11, three at 0.13 and one at 0.36, possibly because these cases were at the lower end of cocaine levels, however, we could not rule out that the hair was contaminated. Whilst it is not possible to differentiate between the drug extracted from the hair and the drug attached to the outside of the hair, we can compare levels of drug in the wash residue with levels detected in the hair sample. In addition, further diagnostic criteria must be applied to minimise potential misdiagnosis of external contamination. When drugs are detected in hair, individuals have clearly been in an environment where drugs are present, but it is only on rare occasions that it is unclear whether this is the result of drug use or of external contamination, and, in those cases, the results of testing need to be interpreted in the light of corroborating evidence from clinical data or social context.

Comparison and validation of screening tools for substance use in pregnancy: a cross-sectional study conducted in Maryland prenatal clinics

IntroductionPrescription-drug use in the USA has increased by more than 60% in the last three decades. Prevalence of prescription-drug use among pregnant women is currently estimated around 50%. Prevalence of...

Disappearance of R/S-methamphetamine and R/S-amphetamine from human scalp hair after discontinuation of methamphetamine abuse

Methamphetamine (MA) and amphetamine (AM) are widely abused drugs. These compounds contain a chiral center, and their enantiomers exhibit different pharmacologic, pharmacokinetic, and metabolic properties due to differences in binding affinities to their receptor sites. Until now, there was a lack of information on the decline in the concentration of drugs in hair after abstinence. A simple procedure for the chiral separation and determination of methamphetamine (MA) and its metabolite amphetamine (AM) enantiomers by LC–MS/MS in hair samples has been developed and fully validated. The LODs and LLOQs were 0.02ng/mg and 0.05ng/mg for all analytes, respectively. This method was successfully applied to both real hair specimens from chronic MA users and after the discontinuation of MA. The concentration of total MA, and total AM in fifty-eight authentic hair specimens ranged from 7.8ng/mg to 521.0ng/mg, and from 0.3ng/mg to 84.0ng/mg, respectively. Both enantiomers of MA and/or AM were detected in seven of fifty-eight authentic hair specimens. Hair specimens were from thirteen women with a known history of MA abuse, who went to a rehabilitation center and ceased consuming MA (for 4–5 months). The S-isomers of MA and AM were detected in all the 5–6cm segments. Both enantiomers of MA were detected in nine of the 5–6cm segments and the enantiomers of AM were found in only five of the nine samples. Assuming a hair growth rate of 1cm/month, the mean hair elimination half-lives of S-MA, R-MA, S-AM, and R-AM were 0.64(95% CI, 0.46–0.96), 0.58(95% CI, 0.41–0.93), 0.62(0.49–0.88), and 0.50 months (95% CI, 0.42–0.56), respectively. With the developed method, R/S-MA and R/S-AM could be detected in the hair of former drug users for approximately 4 months after abstinence. S-MA is the most commonly found analyte in hair segments and is principally used by abusers. Our results suggest that to evaluate the discontinuation of MA abuse after a 6-month period of abstinence, a 3-cm proximal hair segment should be free of MA at the SOHT proposed cut-off level.

Saçta İlaç ve Madde Birikimi

Son yıllarda saç; adli toksikoloji, klinik toksikoloji ve klinik kimya alanlarındaki uyuşturucu testinde rutin kullanılan kan ve idrar örneklerine alternatif olan temel bir biyolojik örnek hâline gelmiştir. Saçlarda kötüye kullanılan ilaçların analitik sonuçları, kronik uyuşturucu kullanımı hakkında yararlı bilgiler sağlamaktadır. Sonuçlar, kişilerin uyuşturucu istismarının geçmişini ve ciddiyetini tahmin etmek için değerlidir ve idrar uyuşturucu analizinin yorumlanmasını kolaylaştırmak için uyuşturucu kullanımı hakkında ek bilgi temin etmektedir. Saç analizi geniş tespit penceresine sahiptir. Örnek toplanması invaziv değildir. Saç örneklerinin bir diğer avantajı, oda sıcaklığında saklanabilmeleri ve toplamadan sonra hızlıca analiz edilmesine gerek duyulmamasıdır. Ayrıca saç analizinin gebelikte ilaç veya madde maruziyetinin saptanmasında, doping kontrolünde, alkol kullanım bozukluklarının saptanmasında kullanılabileceği belirlenmiştir. İlaçlar veya maddelerin melaninler, lipitler ve proteinler gibi hücre içi bileşenlere bağlanarak saç içine dâhil olduğu bildirilmiştir. Saçın oluşumu sırasındaki başlıca üç etkenin (kan akımının, ter ve sebum, dış ortam) madde veya ilaçların saçta birikiminde etkili olduğu öne sürülmüştür. Bu çalışmada, saçta ilaç veya madde birikim mekanizmalarının ve birikimi etkileyen faktörlerin, saç analizinin uygulama alanlarının belgelemesi ve tartışılması amaçlanmıştır.

Quantitative analysis of drugs in hair by UHPLC high resolution mass spectrometry

Liquid chromatographic methods coupled to high resolution mass spectrometry are increasingly used to identify compounds in various matrices including hair but there are few recommendations regarding the parameters and their criteria to identify a compound. In this study we present a method for the identification and quantification of a range of drugs and discuss the parameters used to identify a compound with high resolution mass spectrometry.Drugs were extracted from hair by incubation in a buffer:solvent mixture at 37°C during 18h. Analysis was performed on a chromatographic system comprised of an Agilent 6550 QTOF coupled to a 1290 Infinity UHPLC system. High resolution accurate mass data were acquired in the All Ions mode and exported into Mass Hunter Quantitative software for quantitation and identification using qualifier fragment ions.Validation included selectivity, matrix effects, calibration range, within day and between day precision and accuracy. The analytes were 7-amino-flunitrazepam, 7-amino-clonazepam, 7-amino-nitrazepam, acetylmorphine, alimemazine, alprazolam, amphetamine, benzoylecgonine, buprenorphine, diazepam, ethylmorphine, fentanyl, hydroxyzine, ketobemidone, codeine, cocaine, MDMA, methadone, methamphetamine, morphine, oxycodone, promethazine, propiomazine, propoxyphene, tramadol, zaleplone, zolpidem, and zopiclone. As proof of concept, hair from 29 authentic post mortem cases were analysed.The calibration range was established between 0.05ng/mg to 5.0ng/mg for all analytes except fentanyl (0.02–2.0), buprenorphine (0.04–2.0), and ketobemidone (0.05–4.0) as well as for alimemazine, amphetamine, cocaine, methadone, and promethazine (0.10–5.0). For all analytes, the accuracy of the fortified pooled hair matrix was 84–108% at the low level and 89–106% at the high level. The within series precisions were between 1.4 and 6.7% and the between series precisions were between 1.4 and 10.1%.From the 29 autopsy cases, 121 positive findings were encountered from 23 of the analytes in concentrations similar to those previously published.We conclude that the developed method proved precise and accurate and that it had sufficient performance for the purpose of detecting regular use of drugs or treatment with prescription drugs. To identify a compound we recommend the use of ion ratios as a complement to instrument software “matching scores”.

Hair analysis for the detection of drug use-is there potential for evasion?

Hair analysis for illicit substances is widely used to detect chronic drug consumption or abstention from drugs. Testees are increasingly seeking ways to avoid detection by using a variety of untested adulterant products (e.g., shampoos, cleansers) widely sold online. This study aims to investigate adulteration of hair samples and to assess effectiveness of such methods. The literature on hair test evasion was searched for on PubMed or MEDLINE, Psycinfo, and Google Scholar. Given the sparse nature of peer-reviewed data on this subject, results were integrated with a qualitative assessment of online sources, including user-orientated information or commercial websites, drug fora and "chat rooms". Over four million web sources were identified in a Google search by using "beat hair drug test" and the first 86 were monitored on regular basis and considered for further analysis. Attempts to influence hair test results are widespread. Various "shampoos," and "cleansers" among other products, were found for sale, which claim to remove analytes. Often advertised with aggressive marketing strategies, which include discounts, testimonials, and unsupported claims of efficacy. However, these products may pose serious health hazards and are also potentially toxic. In addition, many anecdotal reports suggest that Novel Psychoactive Substances are also consumed as an evasion technique, as these are not easily detectable via standard drug test. Recent changes on Novel Psychoactive Substances legislations such as New Psychoactive Bill in the UK might further challenge the testing process. Further research is needed by way of chemical analysis and trial of the adulterant products sold online and their effects as well as the development of more sophisticated hair testing techniques.

Quantification of 11-nor-9-carboxy-THC and panel of 22 drugs in hair using a hybrid triple quadrupole linear ion trap mass spectrometer (QTRAP)

The goal of this study was to develop a mass spectrometric method that reproducibly detects and quantifies 11-nor-9-Carboxy-THC levels in hair below 0.2 pg/mg. Using the same QTRAP system, a method was evaluated that allows the identification with simultaneous quantification and confirmation through MS/MS library matching and ion ratio values, for a panel of commonly analyzed forensic drugs in hair. Sample preparation of 11-nor-9-Carboxy-THC consisted of a methanol/water wash followed by a NaOH digest at 75 °C for one hour and then hexane/ethyl acetate liquid extraction. For the other compounds an overnight acetonitrile/formic acid digest was used. HPLC separation used a reverse-phase column at 30 °C, using 8.0 minute gradient. A SCIEX 6500 + QTRAP system in MRM3 mode was used for 11-nor-9-Carboxy-THC detection and MRM (two transitions per analyte) with Information Dependent Acquisition (IDA)-triggering enhanced product ion (MRM-IDA-EPI) scans for analysis of all other analytes. Detection of 11-nor-9-Carboxy-THC in hair by MRM is hampered by the complexity of the matrix and presence of compounds of similar structure and mass. This often leads to high background and interfering peaks in the MRM trace that does not allow the low detection requirements. In order to eliminate these interferences and background to improve the LOQ with good reproducibility, MRM3 fragmentation has the required selectivity to allow for the low level quantification. We will show that at the 0.2 pg/mg cutoff level in MRM mode the 11-nor-9-Carboxy-THC is hardly detectable in the high background and multiple interfering peaks but easily detectable using the MRM3 approach. We were able to quantifiy 11-nor-9-Carboxy-THC levels in hair down to 0.04 pg/mg with 99% accuracy and less than 11% CV. A scheduled MRM-IDA-EPI experiment was developed to detect and confirm the presence of analytes from a targeted 22 compound panel in hair. The experiment allowed the simultaneous confirmation via MS/MS library matching (scores > 75% for all compounds) and ion ratios (<20% CV for all analytes) as well as successful quantification of each compound in the panel with high precision. This was achieved by scheduling the MRM transitions and maximizing the time spent acquiring quality full scan MS/MS data to use in library searching. Linearity was from 5 pg/mg to 2.5 ng/mg for all compounds. We developed a MRM3 method that reproducibly detects and quantifies 11-nor-9-Carboxy-THC levels in hair down to 0.04 pg/mg. We also developed a QTRAP method allowing simultaneous identification quantification and confirmation for a panel of 22 forensic drug compounds. For Research Use Only. Not for use in diagnostic procedures.

Matrix-assisted laser desorption/ionization mass spectrometric imaging for the rapid segmental analysis of methamphetamine in a single hair using umbelliferone as a matrix

Segmental hair analysis offers a longer period for retrospective drug detection than blood or urine. Hair is a keratinous fiber and is strongly hydrophobic. The embedding of drugs in hydrophobic hair at low concentrations makes it difficult for extraction and detection with matrix-assisted laser desorption/ionization (MALDI) coupled with mass spectrometric imaging (MSI). In this study, a single scalp hair was longitudinally cut with a cryostat section to a length of 4 mm and fixed onto a stainless steel MALDI plate. Umbelliferone was used as a new hydrophobic matrix to enrich and assist the ionization efficiency of methamphetamine in the hair sample. MALDI-Fourier transform ion cyclotron resonance (FTICR)-MS profiling and imaging were performed for direct detection and mapping of methamphetamine on the longitudinal sections of the single hair sample in positive ion mode. Using MALDI-MSI, the distribution of methamphetamine was observed throughout five longitudinally sectioned hair samples from a drug abuser. The changes of methamphetamine were also semi-quantified by comparing the ratios of methamphetamine/internal standard (I.S). This method improves the detection sensitivity of target drugs embedded in a hair matrix for imaging with mass spectrometry. The method could provide a detection level of methamphetamine down to a nanogram per milligram incorporated into hair. The results were also compared with the conventional high performance liquid chromatography -tandem mass spectrometry (HPLC-MS/MS) method. Changes in the imaging results over time by the MSI method showed good semi-quantitative correlation to the results from the HPLC-MS/MS method. This study provides a powerful tool for drug abuse control and forensic medicine analysis in a narrow time frame, and a reduction in the sample amount required.

High-throughput screening for drugs of abuse and pharmaceutical drugs in hair by liquid-chromatography-high resolution mass spectrometry (LC-HRMS)

A liquid chromatography–high resolution mass spectrometry (LC-HRMS) method for the simultaneous screening in hair samples of drugs of abuse and medicaments was developed. Target analytes screened using a single extraction and analytical run were opiates, cocaine, amphetamines and amphetamine-like substances, ketamine and analogues, cannabinoids, both natural and synthetic, cathinones, piperazines, ephedrines and others new psychoactive substances not pertaining to these classes; pharmaceutical drugs such as antipsychotics, antiepileptics, antidepressants, benzodiazepines and analogues, anorectics, stimulants, drugs for the erectile dysfunction.The multiresidual method involved methanolic incubation of 30mg of decontaminated hair and analysis of the extract in HPLC using a C18 column. The mass detector, a benchtop Orbitrap Exactive, with nominal resolving power of 100,000, operated in full scan mode in positive ESI. Analytes were identified by exact mass, correspondence of isotopic cluster and retention times using a home-made database. The database contained the protonated exact masses of each monoisotopic compound, the retention time and the molecular formula of each studied analyte. At the moment the database contains 177 analytes. The screening method was validated for selectivity, limit of detection (LOD), matrix effect and carryover. The limits of detection obtained varied from 2 to 30pg/mg, and the matrix effect was negligible.This method was then applied to three hundred authentic samples, resulting in the identification of various drugs of abuse and therapeutic drugs. The analyte identity was subsequently confirmed by in-source fragmentation. Thanks to the scan acquisition, this method also enables retrospective re-analysis of the acquired datafile in case a further analyte needs to be screened.

Assessment of rates of recanting and hair testing as a biological measure of drug use in a general population sample of young people.

AimsWe investigate the extent of and factors associated with denial of previously reported cannabis and other illicit drug use, and assess the potential of hair testing for measuring substance use in general population samples.DesignBirth cohort study.SettingUnited Kingdom, 1991–present.ParticipantsA total of 3643 participants who provided hair and self‐report measures of cannabis and other illicit drug use in the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 18 years.MeasurementsDenial of ever use of cannabis and other illicit drugs at age 18 following previously reported use. Positive hair drug tests for cannabis and other illicit drugs, and expected numbers of false positives and false negatives based on expected sensitivity and specificity.FindingsCannabis and other illicit drug use was reported by 1223 and 393 individuals, respectively, before age 18 years. Of these 176 (14.4%) and 99 (25.2%), respectively, denied use at age 18. Denial of cannabis use decreased with the reporting of other substances and antisocial behaviour. Cannabis and other illicit drug use at age 18 was reported by 547 (22.5%) and 203 (8.4%) individuals, respectively. Of these, 111 (20.3%) and 13 (6.4%) were hair‐positive for cannabis and other illicit drugs, respectively. Based on hair testing for cannabis use we expect 0 [95% confidence interval (CI) = 0–169] false positives and 394 (95% CI = 323–449) false negatives compared to observed 362 potential false positives and 436 potential false negatives based on self‐report. In hair‐positive individuals, reporting the use of other substances and antisocial behaviour decreased the odds of a negative self‐report.ConclusionsHair analysis provides an unreliable marker of substance use in general population samples. People who report more frequent substance use before age 18 are less likely to later deny previous substance use at age 18 than people who report occasional use.

Targeted analysis of 116 drugs in hair by UHPLC-MS/MS and its application to forensic cases.

A multi-target method that can detect a broad range of drugs in human hair, such as hypnotics, anxiolytics, analgesics, benzodiazepines, antihistamines, antidepressants, antipsychotics, and anticonvulsants, was developed based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The drugs were extracted from 10 mg of washed hair by incubation for 18 h in a 25:25:50 (v/v/v) mixture of methanol/acetonitrile/2 mM ammonium formate (8% acetonitrile, pH 5.3). For 51% of the basic drugs, the lower limits of quantification (LLOQs) were in the range of 0.05-0.5 pg/mg, and the majority (98%) were ≤ 5 pg/mg. Linearity ranged from LLOQs to 100-500 pg/mg for all the basic drugs. For acid and neutral drugs, the LLOQs ranged from 0.4 to 500 pg/mg, and linearity ranged from LLOQs to 80-40 000 pg/mg. According to published reports on concentrations attained in single dose control studies, the present method is sensitive enough to detect single-dose drug exposure for many of the drugs. The accuracy was within 75-125% for the majority of drugs. Good precision was observed (relative standard deviations [RSD%] < 25%) for most of the compounds, including the prepared quality control (QC) hair samples. The method was applied to forensic cases and concentrations of rarely reported drugs in hair in 25 post-mortem forensic cases were presented. Hair concentrations of amisulpride, gabapentin, mianserin, mepyramine, orphenadrine, and xylometazoline have not been previously reported. Copyright © 2016 John Wiley & Sons, Ltd.

Cutaneous Side Effects and Transepidermal Water Loss To Gefitinib: A Study of 11 Patients.

IntroductionCutaneous side effects caused by epidermal growth factor receptor (EGFR) inhibitors occurred in 45–100% of patients which may lead to therapy modification or interruption. This study aimed to evaluate cutaneous side effects and transepidermal water loss (TEWL) values in non-small cell lung carcinoma (NSCLC) patients who received gefitinib EGFR inhibitor.MethodsA descriptive observational study with cross-sectional design and a consecutive sampling method was conducted from 1 February to 4 March 2016. Eleven NSCLC patients with EGFR mutation who visited the Hemato-Oncology Clinic/Internal Medicine Department, Dr. Hasan Sadikin General Hospital, Bandung, Indonesia, were assessed through history taking, physical examination, and TEWL examination using Tewameter.ResultsTen of the eleven patients experienced cutaneous side effects. The most frequently observed was xerosis cutis (8/10 patients), followed by acneiform eruptions (7/10 patients), and paronychia (3/10 patients). None of these patients experienced hair changes, mucositis, or drug hypersensitivity. Mean TEWL value of these patients was higher than normal (11.205 ± 1.881 g/m2/h).ConclusionsPatients who received gefitinib EGFR inhibitor experienced cutaneous side effects including xerosis cutis, acneiform eruptions, and paronychia, and have mean TEWL values higher than normal. Therefore, it might affect the skin barrier function.Electronic supplementary materialThe online version of this article (doi:10.1007/s13555-016-0163-0) contains supplementary material, which is available to authorized users.

Identification and quantification of 4-methylethcathinone (4-MEC) and 3,4-methylenedioxypyrovalerone (MDPV) in hair by LC–MS/MS after chronic administration

4-Methylethcathinone (4-MEC) and 3,4-methylenedioxypyrovalerone (MDPV) are synthetic cathinones. The objective of this study was to develop a method in order to measure these compounds in hair of a patient. After decontamination, 20mg of hair were grinded and incubated in phosphate buffer pH 5.0 in presence of 100ng of MDMA-d5 used as internal standard. Double basic liquid–liquid extraction was performed. Samples were separated on a 1.9μm Hypersil GOLD PFP column (100×2.1mm) using gradient elution. Compounds were detected by a LCQ TSQ Vantage XP triple-quadrupole mass spectrometer. SRM transitions m/z 192.1→146.1 and 174.2, m/z 276.1→175.0 and 205.1 and m/z 199.1→165.1 were used for 4-MEC, MDPV and IS, respectively. The assay was accurate and precise over the range 0.001 (lower limit of quantification) to 1ng/mg in hair. No matrix effect was observed. The method has been applied to a 30-year-old man who usually consumed cathinones for 6 months administered intravenously and was admitted to a general hospital for delirious and tachycardia after absorption of 10g of a powder sold as 4-MEC and 5g of MDPV. Both 4-MEC (30ng/mg) and MDPV (1ng/mg) were identified in the hair at high concentrations showing a regular consumption of these drugs. Many others compounds were also identified (mephedrone, MDMA, MDA, cocaine and metabolites, tramadol, hydroxyzine, aripiprazole, haloperidol). Few data are available on concentration of these new designer drugs in hair however important in order to determine the acute or chronic consumption of these drugs.

Three-step drug extraction from a single sub-millimeter segment of hair and nail to determine the exact day of drug intake

Hair and nails are often used to prove drug intake over several months. However, it is impossible to determine the day of drug intake by conventional segmental analysis of bulk samples. To improve this segmental analysis, we prepared accurate 0.4-mm hair and 0.2-mm nail segments, which correspond to their respective growth rates of 1–2 days, using a tissue slicer. The aim of this study was to develop an efficient method to extract drugs from a single sub-millimeter segment of hair and nail. Hair and nails were collected from a subject who was administered a single dose of chlorpheniramine. Four drug extraction methods based on different principles such as sonication, microwaves, micropulverization, and alkaline dissolution were compared. Short-duration sonication followed by long-duration soaking served the aim. Drug extraction from a sub-millimeter segment was performed in three steps as follows: a segment was first washed, followed by sonication for 10 min soaking in the extraction solution for 24 h. The drug concentrations in the three extracts from each segment were quantified using high performance liquid chromatography-tandem mass spectrometry. Each concentration was displayed on a single hair strand and a single nail block so that the first, second, and third extracts corresponded to components on the surface, in the outer layer, and within the sample, respectively. The distribution of chlorpheniramine in a hair successfully reflected the intake history. This method can be used in the future to measure the detailed distribution of drugs in a single hair and nail.

European guidelines for workplace drug and alcohol testing in hair.

Guidelines for Legally Defensible Workplace Drug Testing have been prepared and updated by the European Workplace Drug Testing Society (EWDTS). They are based on the 2010 version published by Pascal Kintz and Ronald Agius (Guidelines for European workplace drug and alcohol testing in hair. Drug Test. Anal. 2010, 2, 367) and in concordance with the Society of Hair Testing guidelines (Society of Hair Testing guidelines for drug testing in hair. Forensic Sci. Int. 2012, 218, 20-24). The European Guidelines are designed to establish best practice procedures whilst allowing individual countries to operate within the requirements of national customs and legislation. The EWDTS recommends that all European laboratories that undertake legally defensible workplace drug testing use these guidelines as a template for accreditation. Copyright © 2016 John Wiley & Sons, Ltd.

Long-term monitoring of opioid, sedative and anti-inflammatory drugs in horse hair using a selective and sensitive LC-MS/MS procedure.

BackgroundCompared to blood or urine, drugs can be detected for much longer periods in the long hair of horses. The aim of this study was to establish and validate a highly sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the detection and quantification of frequently prescribed opioids, sedatives and non-steroidal anti-inflammatory agents in the mane and tail hair of horses. Based on an average growth rate of about 2 cm per month, times of administration reported by horse owners or veterinary physicians were related to drug localizations in hair. Hair samples were collected from ten horses that received drug treatments and analyzed in segments of 2, 4 or 6 cm in length. Hair segments were decontaminated, cut into fragments and methanol-extracted under sonication. The extracts were analyzed by LC-MS/MS for 13 commonly used drugs using the validated procedure. Deuterated analogs were included as internal standards.ResultsAnalytes were detected in hair samples with a length of up to 70 cm. Fourteen out of 16 hair samples were positive for at least one of the tested drugs. Segmentation allowed for time-resolved monitoring of periods of 1 to 3 months of drug administration. Concentrations in dark hair reached a maximum of 4.0 pg/mg for butorphanol, 6.0 pg/mg for tramadol, 1.4 pg/mg for morphine, 1.8 pg/mg for detomidine, 1.2 pg/mg for acepromazine, 39 pg/mg for flunixin, 5.0 pg/mg for firocoxib, and 3’600 pg/mg for phenylbutazone. Only trace amounts of meloxicam were detected. Drug detection correlated well with the reported period of medical treatment. No analytes were detected in the light-colored mane and tail hair samples from one horse despite preceding administrations of acepromazine and phenylbutazone.ConclusionThis study describes a sensitive and selective technique suitable for the validated detection and quantification of frequently prescribed veterinary drugs in horse hair. The segmental method can be applied for time-resolved long-term retrospective drug monitoring, for example in prepurchase examinations of horses as drug detection in hair can prove preceding medical treatments.