Drug Concentrations In Hair Research Articles

Drug Concentrations in Hair and Dried Blood Spots as Preexposure Prophylaxis Adherence Metrics During Pregnancy and Postpartum.

We evaluated hair tenofovir (TFV) concentrations as an adherence metric for HIV preexposure prophylaxis during pregnancy and postpartum and compared hair levels with TFV-diphosphate levels in dried blood spots (DBSs). Overall 152 hair samples from 102 women and 36 hair-DBS paired samples from 29 women were collected from a subset of women in a cluster-randomized trial. Having a partner with HIV was associated with higher hair TFV levels (P < .001). Hair TFV concentrations were strongly correlated with DBS TFV-diphosphate levels (r = 0.76, P < .001), indicating hair as a promising cumulative adherence metric for perinatal preexposure prophylaxis assessment.

Is there a relationship between abuse of alcohol and illicit drugs seen in hair results?

Combined use of alcohol and illicit drugs is a serious health and social problem. In this study, it was examined, whether a relationship between alcohol and drug abuse can be ascertained by comparison of alcohol marker and drug concentrations in hair. In the frame of a social support system for families with parental abuse of illicit drugs, hair samples were analyzed between 2011 and 2022 for methadone, heroin (6-acetylmorphine), cocaine, amphetamine, ecstasy (MDMA), cannabinoids (THC), and the alcohol markers ethyl glucuronide (EtG) and ethyl palmitate (EtPa). For 1314 hair samples from adolescent and adult family members, the hair results show a prevalence of combined occasional or regular drug use and social or abusive alcohol use of 41%-60% except heroin (35%). The drug concentrations were statistically compared in the three categories of abstinence or moderate drinking, social drinking, and alcohol abuse. For the most frequently detected drug cocaine (n = 703), a significant increase of the concentrations with rising alcohol consumption was found. The frequent detection of cocaethylene proved the preferred simultaneous intake of both substances. For THC (n = 489), no significant difference between the alcohol consumer groups was seen. Concerning the less frequently detected methadone (n = 89), 6-acetylmorphine (n = 92), amphetamine (n = 123), and MDMA (n = 105), no clear trend between drug and alcohol marker results was determined. It is concluded that the evaluation of hair results is an appropriate way to study the extent of combined drug-alcohol consumption and complements other studies based on acquisition of consumption data by interview or questionnaire.

Hair analysis: Assessment of homemade hair treatment effects on drug concentrations in the keratin matrix.

Hair is the matrix of choice for investigating a subject's drug history over time, usually with specific forensic applications (license renewal, workplace drug testing, toxicological evaluation), and it is generally considered difficult to be tampered with. Nevertheless, some treatments promising to lower drug concentrations in hair are described online as how to "pass" a drug test. We selected three of these practices, claiming to be effective in decreasing drug concentrations-Treatment 1: (A) baking soda, (B) salicylic acid, (C) bleach; Treatment 2: (A) bleaching and (B) dyeing; Treatment 3: (A) white vinegar, (B) salicylic acid moisturizer, (C) liquid cleanser, and (D) dyeing. Quantitative results were compared with those of untreated hair strands, used as reference. We evaluated the efficacy of the treatment on drugs of abuse and benzodiazepines. Treatment 1 proved to be the most effective, since drug concentrations in treated hair were significantly lower than in untreated ones, although methadone and tetrahydrocannabinol (THC) seemed to be less affected than cocaine and 6-monoacetylmorphine (MAM). The mean percentage values of treatment-induced decrease were up to 90% for cocaine, 81% for benzoylecgonine, 77% for morphine, 89% for MAM, 37% for methadone, 67% for ketamine, 80% for MDMA, 76% for methamphetamine, and 60% for THC, compared with the reference samples. There was no noticeable damage or discoloration of the keratin matrix, making it difficult for the technicians to determine if there was a treatment. This could be an issue for the application of cutoffs or when low concentrations of drugs are incorporated into the keratinic matrix.

Evaluation of applicability of micro-segmental analysis to hair treated with heat and haircare products.

Micro-segmental analysis (MSA), which enables the measurement of detailed drug distributions in hair by segmenting a single hair strand at 0.4mm intervals, is indispensable for estimating the day of drug ingestion. However, haircare with dryers and various products can influence drug concentrations in hair. Therefore, the applicability of MSA to hair that was treated with heat or various haircare products was evaluated. Reference hair strands containing drugs consistently along the hair shafts were collected from patients who ingested four hay-fever medicines (fexofenadine, epinastine, cetirizine, and loratadine) daily for 4months. The hair strands were divided into eight 4mm regions from the proximal end, and each region was placed on an electric hot plate at 100-200°C or soaked in haircare products, such as shampoo and bleaching agent. The hair regions were subjected to MSA. Moreover, after a patient was administered midazolam at a single dose and the hair was bleached, the day of midazolam administration was estimated using MSA. Repetitive heating for 1min and daily haircare products, such as shampoo, hardly affected the drugs in hair, whereas bleaching products containing H2O2 decreased the amounts of hay-fever medicines in the hair up to 58%. However, the amount of midazolam did not decrease in bleached hair and the day of midazolam administration was successfully estimated. The analytes used in this study were minimally affected by ordinary haircare and could be detected even in bleached hair. Therefore, MSA can be applicable regardless of haircare history.

Detection of drugs and metabolites in hair before and after treatment with freely available agents chosen to effectively remove drugs from the hair matrix – A case study

Hair analysis is commonly used to control abstinence or provide evidence for drug use or drug exposure. While dyeing and coloration of hair have been proven to potentially reduce drug concentrations in hair, relatively little is known about the reduction of drug concentrations after extensive use of ‘household remedies’. In this study, a male subject with known past drug intake applied multiple washing procedures including the use of egg yolk, olive oil and vinegar in addition to common hair shampoo for one week in order to intentionally reduce drug concentrations in hair. Solutions with varying compositions were applied to the head for one hour per day. Hair samples were taken before and after the washing procedure from different parts of the skull. For drug analysis the samples were divided into two segments (0–3 cm and 3–6 cm). The analyses comprised methanol extraction and LC-MS/MS detection of cocaine and metabolites, designer stimulants, opioids and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) as well as alkaline hydrolysis followed by liquid-liquid extraction and GC MS/MS detection for Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN). The following drugs or drug metabolites were detected in the hair samples before the washing procedure in accordance with the information given by the subject: cocaine, benzoylecognine, cocaethylene, amphetamine, MDMA, nortilidine, 3-fluorophenmetrazine, ketamine, norketamine and the cannabinoids THC, CBD, CBN and THC-COOH. The concentrations differed depending on the location of hair sampling. After the washing procedure, drug concentrations in hair were significantly reduced (up to about 70%). In some cases, the drug concentrations fell below the values mentioned in the ‘CTU’ criteria for driving liability diagnostics. It is possible to significantly reduce drug concentrations in hair with products available for everyone. In cases with initial drug concentrations close to ‘cut-off’ values, such procedures might lead to ‘false negative’ results.

Evaluating the reliability of hair analysis in monitoring the compliance of ADHD patients under treatment with Lisdexamphetamine.

Considering the high clinical and forensic relevance of pharmaco-adherence during lisdexamphetamine (LDX) treatment for attention-deficit/hyperactivity disorder (ADHD), the aim here was to evaluate hair analysis as a tool for monitoring compliance in patients currently undergoing long term treatment with LDX, by detecting possible interruptions of medication intake or changes in dosage. For this purpose, a total of 24 patients from an outpatient clinic for ADHD were recruited. Hair and urine samples were taken after three consecutive therapy sessions over a 7-month period and analyzed for amphetamine (AMP) enantiomers and other drugs, using chiral and achiral liquid chromatography-tandem mass spectrometry (LC-MS/MS). Participants also provided information on the condition of their hair, the consumption of illegal psychotropic substances and the regularity of taking LDX. Two participants withdrew from the study early. Urine analyses were positive for D-AMP in all urine samples and therapy sessions, except in two patients who did not take LDX on a daily basis. D-AMP was detected in all hair samples; however, no correlation was found between prescribed dose/day and D-AMP concentrations in proximal hair segments. Qualitative interpretation of hair analysis showed that 18 of the 22 study completers were compliant concerning the intake of LDX without additional consumption of illegal D,L-AMP. Analysis of urine taken during the therapy sessions showed no correlation between D-AMP concentrations and prescribed dosage, with or without normalization for creatinine. In conclusion, chiral LC-MS/MS hair analysis might represent a non-invasive way to confirm LDX use within the approximate period covered by the hair segment tested, but it does not allow for quantitative therapeutic drug monitoring because of interindividual variability of concentrations in hair. Drug concentrations in hair at different stages of long-term treatment should thus be interpreted with caution by clinicians and forensic experts alike when making assessments of treatment adherence.

Measuring TB drug levels in the hair in adults and children to monitor drug exposure and outcomes.

INTRODUCTION: Testing for anti-TB drugs in small hair samples may serve as a non-invasive tool to measure cumulative drug exposure and/or adherence, as these determine treatment success. We aimed to assess how well hair assays of TB drugs predict TB treatment outcomes.METHODS: A small thatch of hair, ~30 strands, was cut from the occipital region in adults and children from a prospective TB cohort in India. Isoniazid (INH), acetyl-INH and pyrazinamide (PZA) were extracted from the hair samples and quantified using liquid-chromatography-tandem mass spectrometry. The relationship between drug concentrations in hair and time to unfavourable outcomes was assessed using Cox-proportional hazards regression models.RESULTS: A two-fold increase in hair acetyl-INH concentrations in the 264 participants in our cohort with hair assays for TB drugs indicated a lower hazard of unfavourable TB treatment outcomes (aHR 0.67, 95%CI 0.44-1.02) and TB treatment failure (aHR 0.65, 95%CI 0.42-1.01). Higher summed concentrations (a summed measure of INH and acetyl-INH) indicated a lower hazard of treatment failure (aHR 0.69, 95%CI 0.45-1.05)CONCLUSION: Hair levels of INH and its metabolite may predict TB treatment outcomes, indicating the potential utility of this measure to assess and optimise TB treatment outcomes.

Hair as a matrix in monitoring drug epilepsy therapy.

Hair is considered an efficient tool to investigate drug-related histories; thus, the selection of the method of sample preparation is important to obtain a reliable result. The aim of this study was to compare two methods of hair preparation (cutting and pulverizing) to analyse levetiracetam concentration in hair. An additional aim was to evaluate the potential usefulness of the levetiracetam concentration measured as an index of a dosing schedule. Four groups of 12 rats were included in the experiment. Depending on the group, the rats received 10mg/kg of levetiracetam intraperitoneally every 24, 48 and 72hours for 30days. The control group was not treated. At the end of the drug administration, the rats' hair was shaved, cut or pulverized and analysed by the LC/MS-MS method to determine the concentration of levetiracetam. A stronger correlation between the mean hair levetiracetam concentration in hair and the number of drug doses was found in pulverized hair than in cut hair. A smaller standard deviation between the results was obtained in the case of pulverized hair. The results indicate that pulverization gives a more reliable result of drug concentration in hair than cutting and that drug concentration in hair can reflect the scheme of levetiracetam administration.

Development and validation of a liquid chromatography-tandem mass spectrometry method for quantifying delamanid and its metabolite in small hair samples

New all-oral regimens for rifampin-resistant tuberculosis (RR-TB) are being scaled up globally. Measurement of drug concentrations in hair assesses long-term drug exposure. Delamanid (DLM) is likely to be a key component of future RR-TB treatment regimens, but a method to describe its quantification in hair via liquid chromatography-tandem mass spectrometry (LC-MS/MS) has not previously been described. We developed and validated a simple, fast, sensitive, and accurate LC-MS/MS method for quantifying DLM and its metabolite DM-6705 in small hair samples. We pulverized and extracted two milligrams of hair in methanol at 37 °C for two hours, and diluted 1:1 with water. A gradient elution method eluted DLM, DM-6705, and the internal standard OPC 14714 within 3 min, bringing overall analysis time to 5.5 min. The method has limits of detection (LOD) of 0.0003 ng/mg for DLM and 0.003 ng/mg for DM-6705. The established linear dynamic ranges are 0.003–2.1 ng/mg and 0.03–21 ng/mg for DLM and DM-6705, respectively. Eleven of 12 participant hair samples had concentrations within DLM’s linear dynamic range, while all 12 samples had concentrations within the quantifiable range for DM-6705. The ranges of concentrations observed in these clinical samples for DLM and DM-6705 were 0.004–0.264 ng/mg hair and 0.412–12.041 ng/mg hair respectively. We demonstrate that while DLM was detected in hair at very low levels, its primary metabolite DM-6705 had levels approximately 100 times higher. Measuring DM-6705 in hair may accurately reflect long-term adherence to DLM-containing regimens for drug-resistant TB.

A Comprehensive Multi-Analyte Method for Hair Analysis: Substance-Specific Quantification Ranges and Tool for Task-Oriented Data Evaluation.

The aim of the present study was to quantify a large number of analytes including opioids, stimulants, benzodiazepines, z-drugs, antidepressants and neuroleptics within a single sample workup followed by a single analytical measurement. Expected drug concentrations in hair are strongly substance dependent. Therefore, three different calibration ranges were implemented: 0.5 to 600 pg/mg (group 1), 10 to 12,000 pg/mg (group 2) and 50 to 60,000 pg/mg (group 3). In order to avoid saturation effects, different strategies were applied for selected transitions including the use of parent mass ions containing one or two 13C-isotopes and detuning of the declustering potential and/or collision energy. Drugs were extracted from pulverized hair by a two-step extraction protocol and measured by liquid chromatrography--tandem mass spectrometry (LC--MS-MS) using Scheduled MRM™ Algorithm Pro. In total, 275 MRM transitions including 43 deuterated standards were measured. The method has been fully validated according to international guidelines. A MultiQuant™ software based tool for task-oriented data evaluation was established, which allows extracting selected information from the measured data sets. The matrix effects and recoveries were within the allowed ranges for the majority of the analytes. The lower limits of quantification (LLOQs) were for ∼72% of the analytes in the low-pg/mg range (0.5-5 pg/mg) and for ∼24% of the analytes between 10 and 50 pg/mg. These LLOQs considered cut-offs by the Society of Hair Testing (SoHT), if recommended. The herein established multi-analyte approach meets the specific requirements of forensic hair testing and can be used for the rapid and robust measurement of a wide range of psychoactive substances. The analyte-specific wide concentration ranges open up a wide field of applications.

Liquid chromatography–mass spectrometry method for the quantification of corticosteroids, β2-adrenoreceptor agonists and anticholinergics in human hair

Pharmacological treatments of asthma and chronic obstructive pulmonary disease include medications such as inhaled corticosteroids, long- or short-acting β2-adrenoreceptor agonists and anticholinergics. There is an unmet need for the monitoring of adherence and drug exposure to those therapies since poor adherence and/or inhalation technique may impact the control of the disease and the pharmacological strategy. Since plasma therapeutic drug monitoring only reflects the body exposure in the last few hours, the measurement of hair drug concentrations may be of great interest to assess the chronic exposure. A liquid chromatography – tandem mass spectrometry method was therefore developed for the quantification of corticosteroids, β2-adrenoreceptor agonists and anticholinergics in human hair. The method was validated according to the European Medicines Agency and Food and Drug Administration guidelines. Sensitivity, accuracy and precision were excellent, allowing the quantification of drugs in the pg/mg range. The method was shown suitable for the analysis of clinical hair samples, demonstrating that it could be used for hair therapeutic drug monitoring in asthma or chronic obstructive pulmonary disease patients.

A population pharmacokinetic model is beneficial in quantifying hair concentrations of ritonavir-boosted atazanavir: a study of HIV-infected Zimbabwean adolescents

BackgroundAdolescents experience higher levels of non-adherence to HIV treatment. Drug concentration in hair promises to be reliable for assessing exposure to antiretroviral (ARV) drugs. Pharmacokinetic modelling can explore utility of drug in hair. We aimed at developing and validating a pharmacokinetic model based on atazanavir/ritonavir (ATV/r) in hair and identify factors associated with variabilities in hair accumulation.MethodsWe based the study on secondary data analysis whereby data from a previous study on Zimbabwean adolescents which collected hair samples at enrolment and 3 months follow-up was used in model development. We performed model development in NONMEM (version 7.3) ADVAN 13.ResultsThere is 16% / 18% of the respective ATV/r in hair as a ratio of steady-state trough plasma concentrations. At follow-up, we estimated an increase of 30% /42% of respective ATV/r in hair. We associated a unit increase in adherence score with 2% increase in hair concentration both ATV/r. Thinner participants had 54% higher while overweight had 21% lower atazanavir in hair compared to normal weight participants. Adolescents receiving care from fellow siblings had atazanavir in hair at least 54% less compared to other forms of care.ConclusionThe determinants of increased ATV/r concentrations in hair found in our analysis are monitoring at follow up event, body mass index, and caregiver status. Measuring drug concentration in hair is feasibly accomplished and could be more accurate for monitoring ARV drugs exposure.

Segmental hair analysis of olanzapine and N-desmethyl-olanzapine in postmortem hair from mentally ill patients by LC–MS/MS

Hair analysis is a useful tool for establishing long-term drug intake. Segmental analysis, in particular, where the hair is cut into defined segments, can potentially provide a calendar of patients’ drug intake as drugs are incorporated into the growing hair through the bloodstream with an average growth rate of 1 cm per month. Forensic investigations of hair require knowledge of typical concentrations of common pharmaceuticals in hair, which are rarely reported. The aim of this study was to provide values for olanzapine and N-desmethyl-olanzapine concentrations in postmortem hair from chronic olanzapine consumers to contribute to the establishment of a reference interval for this drug. We analyzed postmortem head hair samples from 37 suspected mentally ill patients, who were part of the SURVIVE population, a Danish national autopsy-based study. Each sample was cut into 1 cm segments, and up to six segments, corresponding to up to six months of hair growth prior to death, were analyzed depending on the hair length. The hair extracts were analyzed by liquid chromatography tandem mass spectrometry. Olanzapine and N-desmethyl-olanzapine were added to a published and validated method. The 37 patients were 12 females and 25 males aged 25–81 years. Their hair colors varied from blond to black, with the majority brown, thus no trend could be discerned from the hair colors. Drugs other than olanzapine were found in all cases except one, and illicit drugs were found in the hair samples of 38 % of the cases. We report olanzapine concentrations ranging from 0.005–20.9 ng/mg (median 0.128 ng/mg) and N-desmethyl-olanzapine concentrations from 0.027 to 0.187 ng/mg (median 0.068 ng/mg) for all 141 analyzed segments. Metabolite-to-drug ratios ranged from 0.010 to 3.31 (median 0.590). Dose calculations based on prescription pick-up demonstrated no correlation with the concentrations in hair, but olanzapine concentrations in the proximal hair segment correlated significantly with olanzapine concentrations in postmortem blood. Olanzapine concentrations decreased considerably from the proximal to distal segments, emphasizing the importance of reporting the length of the measured hair when reporting drug concentrations in hair. This study can contribute to the establishment of a reference interval for olanzapine and N-desmethyl-olanzapine concentrations in hair by reporting concentrations in hair from chronic consumers.

Concerns on the Misinterpretation of Very Low Drug Concentrations in Hair.

Concerns on the Misinterpretation of Very Low Drug Concentrations in Hair.

Large scale consumption monitoring of benzodiazepines and z-drugs by hair analysis

Benzodiazepines (BDZ) and z-drugs belong to the most frequently prescribed medicines worldwide used for anxiety, epilepsy and sleeping disorders. Due to their pharmacology, they have a high potential for misuse. Hair analysis is being performed for the retrospective monitoring of drug exposure. However, there is a lack of reference values to obtain indication of BDZ/z-drug misuse. Further, there is no consensus on BDZ/z-drug cut-off concentrations above which a hair sample is reported as positive. The objective of the present study was to retrospectively evaluate BDZ/z-drug levels in hair for better interpretation of hair testing results. For this purpose, 4,630 authentic samples (head/body hair) from a heterogeneous cohort in Switzerland tested for the presence of 20 BDZ/BDZ metabolites and three z-drugs by liquid chromatography-tandem mass spectrometry were included. Drug concentrations in hair were statistically evaluated by box-plots in 1,726 positive samples. Further, metabolite-to-parent drug ratios were determined. Zolpidem, diazepam, nordazepam, oxazepam, lorazepam, midazolam, alprazolam, and bromazepam were among the most frequently detected drugs. Generally, drug concentration ranges varied strongly between the lower limit of quantification and 30,000 pg/mg hair. Sixteen BDZ/BDZ metabolites and zopiclone (z-drug) displayed a median below 50 pg/mg which is recommended as cut-off or minimum requirement for the limit of detection (LOD) by institutions. In case of ten drugs even the 75th percentile was below 50 pg/mg. Therefore, we strongly recommend to reconsider whether the use of an equal BDZ/z-drug cut-off is reasonable and whether minimum requirements for LODs should be lowered. The statistical evaluation of BDZ/Z-drug hair concentrations by box-plots can help in the development of analytical methods for hair samples and in the interpretation of BDZ/z-drug hair levels.

Moving Antiretroviral Adherence Assessments to the Modern Era: Correlations Among Three Novel Measures of Adherence.

There is no gold standard for estimating antiretroviral therapy (ART) adherence. Feasible, acceptable, and objective measures that are cost- and time-effective are needed. US adults (N = 93) on ART for ≥ 3months, having access to a mobile phone and internet, and willing to mail in self-collected hair samples, were recruited into a pilot study of remote adherence data collection methods. We examined the correlation of self-reported adherence and three objective remotely collected adherence measures: text-messaged photographs of pharmacy refill dates for pharmacy-refill-based adherence, text-messaged photographs of pills for pill-count-based adherence, and assays of home-collected hair samples for pharmacologic-based adherence. All measures were positively correlated. The strongest correlation was between pill-count- and pharmacy-refill-based adherence (r = 0.68; p < 0.001), and the weakest correlation was between self-reported adherence and hair drug concentrations (r = 0.14, p = 0.34). The three measures provide objective adherence data, are easy to collect, and are viable candidates for future HIV treatment and prevention research.

Food Insecurity Is Associated With Lower Levels of Antiretroviral Drug Concentrations in Hair Among a Cohort of Women Living With Human Immunodeficiency Virus in the United States.

Food insecurity is a well-established determinant of suboptimal, self-reported antiretroviral therapy (ART) adherence, but few studies have investigated this association using objective adherence measures. We examined the association of food insecurity with levels of ART concentrations in hair among women living with human immunodeficiency virus (WLHIV) in the United States. We analyzed longitudinal data collected semiannually from 2013 through 2015 from the Women's Interagency HIV Study, a multisite, prospective, cohort study of WLHIV and controls not living with HIV. Our sample comprised 1944 person-visits from 677 WLHIV. Food insecurity was measured using the US Household Food Security Survey Module. ART concentrations in hair, an objective and validated measure of drug adherence and exposure, were measured using high-performance liquid chromatography with mass spectrometry detection for regimens that included darunavir, atazanavir, raltegravir, or dolutegravir. We conducted multiple 3-level linear regressions that accounted for repeated measures and the ART medication(s) taken at each visit, adjusting for sociodemographic and clinical characteristics. At baseline, 67% of participants were virally suppressed and 35% reported food insecurity. In the base multivariable model, each 3-point increase in food insecurity was associated with 0.94-fold lower ART concentration in hair (95% confidence interval, 0.89 to 0.99). This effect remained unchanged after adjusting for self-reported adherence. Food insecurity was associated with lower ART concentrations in hair, suggesting that food insecurity may be associated with suboptimal ART adherence and/or drug absorption. Interventions seeking to improve ART adherence among WLHIV should consider and address the role of food insecurity.

Increased Social Support Mitigates the Negative Impact of Food Insecurity on Antiretroviral Adherence Among Postpartum Women in Western Kenya (P04-126-19)

ObjectivesAntiretroviral (ARV) adherence is a strong predictor of improved health outcomes and treatment effectiveness among persons living with HIV. Food insecurity and low social support are have been demonstrated to predict reported nonadherence among pregnant women, but the relationship has not been evaluated using an objective indicator of adherence. Therefore, we explored the impacts of social support and food insecurity on ARV adherence using ARV drug concentrations in hair among postpartum Kenyan women living with HIV. MethodsHair samples were collected from 83 HIV + women, a subset from an observational pregnancy cohort study (NCT02974972), on Efavirenz (n = 58) and Nevirapine (n = 25)-based ARVs at nine months postpartum. Hair ARV concentrations were log transformed to approximate a normal distribution. Food insecurity [Individual Food Insecurity Access Scale (IFIAS, 0–27)], social support (Perceived Social Support Scale, 0–40), and quality of life (Short Form 8 Health Survey, 0–40] were recalled for the prior month. These covariables, along with sociodemographic characteristics, were included in a multivariable linear regression model (P < 0.2) and eliminated using a backward stepwise approach (P < 0.1). ResultsMean IFIAS score was 10.0 (± 5.2). Lower food insecurity and greater quality of life were significantly associated with higher hair ARV concentrations. Each point increase in IFIAS and decrease in quality of life was associated with a 13.4% decrease (95%CI: −0.23, −0.05) and 15.7% decrease (95%CI: 0.06, 0.23) in hair levels, respectively. Social support was not significantly associated with ARV adherence in bivariate analysis, but did buffer against the negative impacts of food insecurity on ARV adherence in the final multivariable model (Figure 1). ConclusionsThis study demonstrates that low food insecurity is significantly associated with higher ARV adherence among postpartum women using an objective biomarker, and that social support can buffer the negative effect of food insecurity on adherence. Interventions addressing these modifiable barriers to ARV adherence should be explored to improve adherence among HIV + postpartum women. Funding SourcesThe study was supported by the National Institute of Mental Health and the National Institute of Allergy and Infectious Diseases. Supporting Tables, Images and/or Graphs▪

A multi-analyte approach for the quantification of 116 analytes in hair

Hair analysis is a widely applied retrospective monitoring tool. One major challenge is to monitor a wide range of analytes including e.g. opioids, stimulants, benzodiazepines, Z-drugs, antidepressants and neuroleptics and some metabolites within the same sample workup followed by a single analytical measurement. Analytes were selected according to availability, requirements for our routine casework and local prevalence. The aim of this study was to establish a routine compatible multi-analyte method considering that expected drug concentrations in hair are strongly substance-dependent and usually vary over a wide range. Based on the expected hair concentrations, each drug was assigned to one out of three analyte groups covering different concentration ranges: 0.5 pg/mg–600 pg/mg (group 1), 10–12,000 pg/mg (group 2), and 50–60,000 pg/mg (group 3). The internal standard solution contained 44 deuterated standards. Drugs were extracted from 20 mg washed and pulverized hair by a 2-step protocol [step 1: methanol; step 2: 1 mM aqueous ammonium formate containing 0.1% formic acid/methanol = 1/1 (v/v) by shaking at 10 Hz for 90 min]. Combined extracts were dried, reconstituted and injected into a LC-MS/MS system using a Sciex QTrap 5500 mass spectrometer (positive advanced scheduled MRM mode). Separation was achieved using a Kinetex ® F5 column (100 mm × 2.1 mm, 100 Å, 2.6 μm, Phenomenex) which operated in a Shimadzu Prominence high performance liquid chromatography system (Shimadzu, Duisburg, Germany) at a flow rate of 0.6 mL/min with a total run time of 12 min (mobile phase A: 1 mM ammonium formate buffer with 0.1% formic acid and acetonitrile containing 1 mM ammonium formate buffer and 0.1% formic acid). A method for the quantification of 116 analytes in hair by a 2-step extraction was established. In total, 276 MRM transitions including deuterated standards were measured. Three substance-depending calibration ranges were successfully implemented. Calibration ranges covered up to three orders of magnitude. In order to avoid saturation effects, parent mass ions containing one or two 13C-isotopes were used for selected transitions (14%) and detuning of the declustering potential (DP) was applied for 41% of the transitions. The method has been fully validated according to international guidelines. The matrix effects and recoveries were within the allowed ranges for 89% and 97% of the analytes, respectively. The lower limits of quantification (LLOQs) were for the majority of the analytes in the low-pg/mg-range (0.5–5 pg/mg) and for approx. 23% of the analytes between 10 and 50 pg/mg. These LLOQs considered cut-offs by the SoHT, if recommended. The presented multi-analyte method can be applied e.g. in assessments for abstinence controls (e.g. regranting the driving license). Due to the low LLOQs, the method is also applicable for the detection of single dose drug exposure, e.g. for DFC or DFSA cases. The detection of metabolites even in the low concentration range allows for determination of metabolic ratios, which can be used as indicators to differentiate between drug use and external contamination. The method was successfully applied for international proficiency tests. The herein established multi-analyte approach can be applied in routine hair testing for the rapid and robust measurement of a wide range of psychoactive substances. The analyte-specific wide concentration ranges open up a wide range of application fields.

Illicit drug concentration in hair from children and their families. A two-year retrospective study in an Italian cohort

Children born or living in a familiar environment where illicit drugs are commonly used are exposed to severe health and social risk. The detection of drugs in children biofluids can indicate in utero exposure, systemic ingestion from mother's breast milk, passive or active exposure from caregivers. Hair analysis of children and their relatives is useful to estimate the exposure risk and may be useful in child neglect/child protection cases when contact with drugs of abuse is questioned. The aim of this study is to present and analyze the prevalence and the concentration of illicit drugs in hair samples of children with clinical signs or circumstantial stories of drug exposure, and in hair from their relatives. A retrospective observational study was performed on the hair samples collected in an obstetrician department at the moment of baby delivery, in cases of suspected prenatal drug exposure, and in a paediatric emergency department in cases of children exhibiting symptoms/signs of intoxication or child abuse. Hair samples were analysed at the local forensic toxicology laboratory. Hair samples of children (< 14 years old) and their relatives were collected. After washing, pulverization and solid phase extraction, samples were analyzed by high performance liquid chromatography – high-resolution mass spectrometry, screening for a wide class of psychotropic substances, including cocaine, opiates, opioids, amphetamines and amphetamine-like substances, cathinone and synthetic cathinones, cannabinoids, benzodiazepines, ketamine, Z-drugs. In 100 cases of suspected exposure to drugs, hair from children and their relatives were collected. Prevalence of children with hair positive for illicit drugs was 72%. Hair samples of mothers were collected in 66% of positive cases, with a concordance with child for most of drugs. Hair samples of other relatives were collected in 43% of positive cases. The most frequently detected drugs were cocaine, opiates and opioids, followed by cannabinoids, ketamine and amphetamine-like substances. According to the children age and the match with the drugs detected in the mother hair samples, the main part of cases can be referred to in utero or short-term exposure from the mother's breast milk, while cases due to exposure or ingestion in the family environment are fewer in the selected setting. The concentration of drugs and metabolites were higher in younger children than in their older siblings. Hair analysis is useful for the early identification of child exposure to illicit drugs, to estimate the risk of child neglect in families, and to monitor the outcome of social service interventions.