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Drug detection is crucial for monitoring the concentration of specific drugs in the human body or veterinary animals or the environment. In this study, the phyllosilicate Effenbergerite (BaCuSi4O10) was prepared by solid-state synthesis for electrochemical sensing of ciprofloxacin (CFX), one of the commonly used antibacterial drugs. Effenbergerite is naturally occurring and widely available and was used as a cost-effective material to fabricate a sensor for the rapid electrochemical detection and quantification of ciprofloxacin. The sensor was fabricated by modifying a glassy carbon electrode (GCE) with the synthesized Effenbergerite to obtain BaCuSi4O10/GCE. Powder X-ray diffraction (PXRD), Fourier-transform infra-red spectroscopy (FT-IR), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) were used to characterize the Effenbergerite. Differential pulse voltammetry (DPV) showed that the optimum pH for the electrochemical detection of ciprofloxacin in phosphate buffer solution (PBS) electrolyte using the BaCuSi4O10/GCE sensor was pH 5.5. The linear range has been established to be 0.05–150 µM, and the limit of detection (LOD) was ca. 9 nM. The sensor was investigated in the presence of non-target interferents as well as in the presence of other drugs and was found to be selective toward ciprofloxacin. The pharmaceutical drug, Cifloc 500, analysis was done to establish the method’s reliability and a significantly low standard deviation of 1.74% was achieved. The results indicate that the sensor has application in detecting CFX in natural waters and wastewater effluents.

The main challenge war focused on the detection of acetaminophen drug using a type of AlN nanocage sensor through density functional theory calculations. The interaction between acetaminophen drug and AlN nanocage has, therefore, been studied by DFT to explore a modern drug detection system. The acetaminophen molecule is bonded via its various sites such as the –OH, –C=O, –NH, and –CH3 group to the Al atom in the AlN nanocage. The AlN nanocage enables the adsorption of the acetaminophen greatly energetically desirable. The acetaminophen adsorbs through an electrostatic mechanism on the AlN nanocage. The acetaminophen dramatically decreases HOMO–LUMO and working function from 3.99 to 3.02 eV and 4.50 to 3.45 eV, leading to improved electrical conductivity and electron field emission, respectively. Thus, the AlN nanocage might be both the electronic and work function type sensor for acetaminophen detection. Moreover, our findings revealed that the AlN nanocage would selectively identify the acetaminophen molecule when environmental pollutants are present, such as methanol and so forth.

Density functional theory calculations were performed to inspect the potential application of pristine AlN nanotube (AlNNT) as well as Pd-decorated AlNNT (Pd@AlNNT) in recognition of gabapentin (GB) drug. The sensing response of AlNNT to the GB drug is very small (~ 5.2 at 298 K) attributed to the small adsorption energy (AE) of −0.16 eV. Molecular orbital energy decomposition method (EDA) showed that the contributions of electrostatic attraction, Pauli repulsion, orbital relations, and dispersion forces in the AE are about −0.21, 0.19, −0.11, and −0.09 eV, respectively. A Pd atom preferentially adsorbed over an Al–N bond of the AlNNT, releasing the energy of 2.93 eV. We found that the GB strongly adsorbed on the Pd@AlNNT with AE of −1.29 eV and the sensing response increased to 524.6 by the Pd decoration. Based on the results, the main stabilization contribution to the AE of GB on the Pd@AlNNT comes from the electrostatic attraction based on the EDA analysis. The recovery time was achieved to be 1.8 s for the GB desorption from the Pd@AlNNT surface. Finally, we concluded that the Pd@AlNNT can transform the presence of GB molecules into electrical signal, and it may potentially be applied as an electronic sensor for GB drug detection.

Diosgenin is a plant-derived secondary metabolite mainly present in the members of the plant family Dioscoreaceae. It is a pharmaceutically important compound because of its anti-cancerous, anti-diabetic, anticoagulant, anti-thrombosis, anti-inflammatory, anti-viral, anti-ageing and other properties. Biotechnology provides an opportunity to genetically manipulate cells, tissues, organs or the whole organisms by propagating them in vitro in order to harvest the bioactive compounds. Diosgenin production from botanical sources is being improved by in vitro techniques which include elicitation, genetic transformations and bioconversions. Various techniques have been developed to obtain compounds for drug detection including separation from plants and other natural sources, molecular modelling, synthetic chemistry and combinatorial chemistry. Development in molecular markers determines genetic relationship, genetic linkage map construction, genetic diversity and identification. For rapid clonal propagation and ex situ conservation, the in vitro tools involving plant cell, tissue and organ culture have been well documented for plant-derived diosgenin production. The present review encompasses the wide application of the biotechnological techniques for diosgenin production via elucidating its biosynthetic pathway, in vitro production and mass propagation and elicitation. In addition, molecular marker-mediated diversity assessment of diosgenin containing plant species is also discussed. The review also presents the recent literature to explore the limitations of the relevant studies and future direction of research on production of diosgenin from Dioscorea spp. KEY POINTS: • Critical and updated assessment on sustainable production of diosgenin from Dioscorea spp. • In vitro propagation of Dioscorea spp. and elicitation of diosgenin production. • Diversity assessment of Dioscorea spp. using molecular markers.

We demonstrate the fabrication of a novel magnetic nanohybrid involving the drug molecule 5-aminolevulinic acid (5-ALA) intercalated Gd-Eu layered rare-earth hydroxide (LRH) coated on magnesium ferrite particles (MgFe2O4). The structure, thermostability, morphology, luminescence properties, cytotoxic effect and magnetism are investigated. The 5-ALA intercalated composite may correspond to a monolayered vertical arrangement, and the thermal stability of organics is enhanced after intercalation. The LRH precursor shows red emission of Eu3+ and the maximum emission peak of the composite is at 451 nm, corresponding to the blue emission. The detection of drug molecules can be realized through the change of luminescence. The magnetic nanohybrid shows strong magnetic sensitivity, which provides an easy and efficient way to separate 5-ALA-MgFe2O4@LGd0.95H:Eu0.05 particles from a sol or a suspension system and to carry drugs to targeted locations under an external magnetic field. The cytotoxic effect of MgFe2O4@LRH is observed with a sulforhodamine B (SRB) colorimetric assay, which has low cytotoxic effects on selected cells. The fabrication of novel bifunctional drug carriers based on LRH with magnetic and fluorescent properties has potential applications in drug detection and drug delivery.

In vivo, drug molecules interact with their biological targets (e.g., enzymes, receptors, ion channels, transporters), thereby eliciting therapeutic effects. Assays that measure the interaction between drugs and bio-targets may be used as drug biosensors, which are capable of broadly detecting entire drug classes without prior knowledge of their chemical structure. This Trends article covers recent developments in bio-target-based screening assays for detecting drugs associated with the following areas: illicit products marketed as dietary supplements, food-producing animals, and bodily fluids. General challenges and considerations associated with using bio-target assays are also presented. Finally, future applications of these assays for drug detection are suggested based upon current needs.

Different kinds of new synthetic cannabinoids (SCs) have been continuously developed to evade drug monitoring. Segmental hair analysis offers a longer period for retrospective drug detection compared with blood or urine. In this study, matrix-assisted laser-desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometric imaging (MALDI-FT ICR MSI) was developed for direct identification and imaging of synthetic indole-3-carboxamide cannabinoids in hair samples using the positive ion mode. The target SCs include N-(adamantan-1-yl)-1-pentyl-1H-indole-3-carboxamide (APICA), N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide (5F-AB-PICA), N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide (ADB-PINACA) and N-(1-amino -3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide (5F-ADBICA). The MALDI-MS and MS/MS were first performed on the scraped hair soaked in a mixture of the four SCs after matrix sublimation. This method may provide a detection power for SCs to the 0.1 ng level per 2 cm hair. Target cannabinoids were identified by MS1 and MS2. Matrix deposition methods including airbrush sprayer and sublimation were compared. The method was then applied in revealing the spatial distribution of APICA and 5F-ADBICA in real hair samples from two drug abusers by comparing MS1 and MS2 spectra. The metabolites of APICA and 5F-ADBICA were also presumed to be present in the positive hair samples. Furthermore, a comprehensive comparison between a MALDI-FT ICR MS and a MALDI time-of-flight–MS instrument was performed in detection-sensitivity and specificity for positive real samples. The proposed method provides a powerful tool for drug supervision and forensic medicine analysis in a wide time window, and the sample amount required was also decreased.

Background Oral fluid is a widely studied matrix able to isolate the primary Cannabis constituent THC, facilitating its detection via mass spectrometry, and in most cases link these findings to recent drug use. As an alternative to liquid oral fluid, dried oral fluid spots (DOFS) is a simple and a low-cost sampling technique. It has shown improved stability compared to liquid samples, allowing for the possibility to preserve the specimens under various temperature and humidity conditions. The sampling strategy is straightforward and involves the application of a small quantity of oral fluid aliquot to a paper substrate that is set to air dry allowing for on-site collection at a large-scale demand. The goal of this study is to study THC and CBD extraction from DOFS, applying a previous established protocol for a LC–MS/MS qualitative method validation. Although other drugs of abuse have been included in DOFS methods, this is the first method validation including cannabinoids. An alternative oral fluid extraction method (WAX-S tips) is demonstrated to improve the recovery of the analytes. Methods A pool of blank oral fluid was used to prepare THC and CBD spiked DOFS samples for method validation and application. Spiked oral fluid was used to demonstrate WAX-S tips THC and CBD extraction. All samples were analyzed on a LC–MS/MS instrument. Results The qualitative method validation for THC and CBD confirmation in DOFS included method selectivity, matrix effects ( Conclusions THC and CBD extraction from DOFS showed low recoveries. However, the LC–MS/MS qualitative confirmation of THC and CBD in DOFS could improve cannabinoids screening in oral fluid, as it shows adequate LOD and stability over time. This method has potential for assisting the screening of drivers under possible drug influence by facilitating sample transportation and temporary storage in dried spot form. Additional research is suggested for WAX-S tips extraction and quantitative method validation.

To provide a review of the available data on 3,4-dimethylmethcathinone (3,4-DMMC), its physicochemical properties, detection methods, patterns of abuse and prevalence, biological effects, pharmacodynamics, pharmacokinetics, metabolism, and mechanisms of toxicity have been presented and discussed. An exhaustive literature search was carried out with PubMed, drug use forums and blogs, and sites from governmental agencies. 3,4-DMMC is a synthetic cathinone that was first detected in Europe in 2010. Its recreational use and trade in retail outlets have been prohibited in several countries, but the drug remains readily available for purchase on the Internet. 3,4-DMMC has been considered a very appealing drug to be used in combination with other abuse substances. The drug combines the features of stimulants and psychoactive phenethylamines, displays high affinity for 5-HT2 and adrenergic receptors, inhibits monoamine transporters, specially serotonin transporter, but does not promote a significant 5-HT efflux. Recently, anecdotal reports on its abuse sprang up, and 3,4-DMMC has been detected in several seized products and in blood and urine of abusers. 3,4-DMMC metabolites in the urine of habitual users showed N-demethylation, β-ketoreduction, hydroxylation, and oxidation as the major reactions involved in its biotransformation. There is a wide scope to be explored on the effects of 3,4-DMMC. Clinicians and pathologists should be encouraged to report their findings in scientific literature, as this will aid in evaluating potential detrimental effects of the drug in further clinical and forensic investigations. Further studies on pharmacokinetic properties of 3,4-DMMC are also necessary to improve the methods of drug detection.

Synthetic cannabinoid receptor agonists, commonly referred to as ‘synthetic cannabinoids’ (SCs), gained popularity as recreational drugs due to their cannabis-like effects. The subclass of valine or tert-leucine-derived SCs has dominated the ‘designer drug’ market in recent years and has been associated with several severe intoxication cases. Most SCs are highly lipophilic compounds and are extensively metabolized prior to renal excretion. Hence, for drug detection in urine samples, the major metabolites of new compounds have to be identified first. The aim of this study was to elucidate structure-metabolism relationships (SMRs) of valine and tert-leucine-derived SCs enabling in-depth understanding of their phase I biotransformation and facilitating the prediction of suitable analytical targets for urine analysis. After incubation of 32 different valine/tert-leucine-derived SCs with pooled human liver microsomes (pHLM), the phase I metabolite profile of each compound was characterized using liquid chromatography–quadrupole time-of-flight mass spectrometry. By comparing chemical-structural analogs with the relative abundances of their metabolites, SMRs were studied. The terminal functionality (amide vs. methyl ester), the amino acid side chain (valine vs. tert-leucine), the core ring system (indole vs. indazole), and the N-alkyl side chain (cyclohexyl methyl vs. pentyl vs. 5-fluoropentyl vs. 4-fluorobenzyl) showed distinct differences of metabolic dehalogenation, dehydrogenation, formation of dihydrodiols, hydrolysis, hydroxylation, and N-dealkylation. The presented pHLM approach proved to be an effective tool for systematic investigation of SMRs. The information gained from this work may be useful for predicting potential SC metabolites for urine analysis.

Oral fluid is recognized as an important specimen for drug testing. Common applications are monitoring in substance abuse treatment programs, therapeutic drug monitoring, pain management, workplace drug testing, clinical toxicology, and driving under the influence of drugs (DRUID). In this study, we demonstrate that non-targeted LC-MS/MS with subsequent compound identification by tandem mass spectral library search is a valuable tool for comprehensive detection and confirmation of drugs in oral fluid samples. The workflow developed involves solid-phase extraction and chromatographic separation on reversed phase materials. Mass spectrometric detection is accomplished on a quadrupole–quadrupole-time-of-flight instrument operated with data-dependent acquisition control. The workflow was optimized for 500 μl of neat oral fluid collected with the Greiner Bio-One saliva collection system. The fitness of the developed method was tested and proven by analyzing blank and spiked samples as well as 59 authentic patient samples. We could demonstrate that compounds with logP values in the range 0.5–5.5 are efficiently detected at low nanograms per milliliter concentrations. The true positive and true negative rates of automated library search were equal or close to 100%. The beauty of the non-targeted LC-MS/MS approach is the ability to detect compounds hardly included in routinely applied targeted assays, and this was demonstrated by detecting the synthetic opioid U-47700 in two patient samples. Graphical abstractᅟ Electronic supplementary material The online version of this article (10.1007/s00216-018-1504-x) contains supplementary material, which is available to authorized users.

Non-adherence to antihypertensive treatment is highly prevalent and represents a major factor affecting their effectiveness in hypertensive patients, thus contributing to apparent treatment resistance. It is however often overlooked because the methods to assess non-adherence are mainly subjective, limiting their usefulness in clinical practice. Non-adherence to treatment affects daily patient management, resulting in inappropriate, costly, and potentially harmful treatments and loss of the expected benefits from antihypertensive drugs. Specialized centers now use a combination of objective screening tools. Firstly, snapshots of adherence levels can be provided by analytical drug detection in various biological matrixes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and secondly electronic monitoring systems of drug delivery which provide longitudinal data on adherence. Routine utilization of those tools allows the detection of non-adherence in patients with resistant hypertension, thus enabling implementation of appropriate interventions to improve drug adherence and avoid unnecessary treatment intensification. Other complementary techniques, such as digital health feedback system with ingestible sensors, are currently evaluated. In the context of an increasing burden of uncontrolled and apparent treatment-resistant hypertension, detecting non-adherence to antihypertensive therapy is, as acknowledged by the latest guidelines, a top priority to implement in clinical practice but still faces medical conservatism and disbelief.

The adsorption of acetylsalicylic acid (ASA) on the outer surfaces of a (1 , 1) aluminum nitride single-wall nanotube (AlNNT) was studied by quantum chemical study calculation. The adsorption energy of ASA on the AlNNT surface was calculated about - 15.62 kcal/mol. The more negative adsorption energy is ascribed to the electrostatic interaction of ASA with AlNNT. By absorbing the aspirin drug on the surface of AlNNT, the nanotube electrical conductivity has increased dramatically by about 21.75%, which can be used as a drug detection signal. Based on the polarizable continuum model (PCM) calculation, the AlNNT-ASA complex in water medium is more stable compared with that in the gas medium. Finally, our findings also revealed that the AlNNT would selectively identify the ASA molecule in the presence of environmental pollutants.

We studied the potential application of the pristine and Al-doped graphyne-like BN nanosheets (Al-BN-yne) in 5-fluorouracil (5-FU) drug detection using DFT calculations. The 5-FU drug preferentially adsorbed via its oxygen atom on the B atom of pristine BN-yne with adsorption energy of − 11.7 kcal/mol and no effect on its electronic properties. Replacing a B atom by an Al atom significantly increased the sensitivity and reactivity of BN-yne to the 5-FU drug. Upon the 5-FU interaction with the Al-BN-yne, an energy of 20.3 kcal/mol is released, and the Eg of Al-BN-yne significantly decreased from 4.83 to 3.80 eV, increasing the electrical conductance. Thus, the Al-BN-yne sheet can generate an electronic signal after the 5-FU drug adsorption, being a promising electronic sensor for 5-FU detection. We predicted that the recovery time for 5-FU drug desorption from the Al-BN-yne sheet surface is 0.07 s, demonstrating that it benefits from a short recovery time.

For many decades, synthetic receptors have been used as sensor elements and are a promising alternative to natural receptors, which, despite its great selectivity, are so complex and instable. The rational design of this kind of receptors is currently one of the most researched topics in molecular recognition. Molecular imprinted polymers (MIPs) have become a growing highlight in polymer chemistry, once they possess a wide range of applications and can be used in several environments, due to their high chemical and thermal stability. The aim of this study was to perform a rational design for the MIP preparation, for 3,4-methylenedioxymethamphetamine (MDMA) detection. The theoretical measurements were employed at several stages of the process, using DFT and B3LYP/6-31G(d,p) level of theory, by means of optimization and frequency calculations. Among the several functional monomers tested, the itaconic acid was the most appropriated for MIP preparation with MDMA template, and the proper molar ratio found theoretically was 3:1 (itaconic acid/MDMA). In the preparation of pre-polymerization complex, polar solvents were found to perform a better stabilization, mainly those which are not protic solvents. As cross-linking agents, the better results were obtained for trimethylolpropane trimethacrylate and ethylene glycol dimethacrylate molecules, respectively. Finally, selectivity tests showed a high affinity of the studied MIP for MDMA and chemically similar molecules. The proposal theoretical strategy yielded novel, experimentally testable hypotheses for the design of MIPs. Additionally, from the theoretical point of view, the set of computational analyses presented in this paper constitutes a very useful protocol to predict optimal experimental conditions, which can considerably reduce the time and cost on the MIPs preparation.

Using density functional theory calculations, we investigated the potential application of Al12N12 and B12N12 nanoclusters as an electronic or work function type sensor for acetylsalicylic acid (ASA) drug detection. The drug tends to be adsorbed on the surface of both AlN and BN clusters via its –COOH group with adsorption energies about − 62.8 and − 21.9 kcal/mol, respectively. The AlN nanocluster is neither electronic nor work function based sensor for ASA because of a low sensitivity, and a huge recovery time (~ 9.8 × 1038 s). But the response of BN nanocluster is completely different, and its electrical conductivity is largely increased in the presence of ASA drug due to the large stabilization of LUMO level. We concluded that the BN nanocluster may be a promising candidate to detect the ASA drug with a short recovery time about 109 s and a high electronic sensitivity. As the work function of the BN nanocluster is not affected by the ASA adsorption, it cannot be used as a work function type sensor.

Widespread use of antibiotics for humans and animals health has led to drugs entering the environment, such as lakes and streams worldwide. It is imperative to develop methods to screen these in drinking water supplies. We developed a novel nanoparticles-based probe to detect the β-lactam skeleton 6-APA. Cationic ligand thiopyridine stabilized silver nanoparticles (ThPy-AgNPs) were synthesized and used for chemosensing of the drug 6-aminopenicillanic acid (6-APA). Along with several drugs, during UV–visible titration with ThPy-AgNPs, a distinctive decrease in surface plasmon resonance bands absorbance was observed with 6-APA. The ThPy-AgNPs-based detection system for 6-APA is based on the phenomenon of de-aggregation and is monitored by using UV–visible spectrophotometry and atomic force microscopy measurements. The process is relatively rapid, highly specific and selective for 6-APA when tested against several other drugs. This optical method can recognize 6-APA as low as 1 μM concentration, and drug detection is independent of the pH of media. Moreover, the optimized sensing protocol is able to sense 6-APA in human blood plasma samples and is not altered by presence of other interfering drugs. It is anticipated that this method will be of immense value to detect 6-APA for blood samples and drinking water.

We inspected the possibility of using a synthesized boron nitride nanocluster (B12N12) as a potential chemical sensor for anticancer α-cyano-4-hydroxycinnamic acid (CHC) drug by performing density functional theory calculations. It was found that CHC drug is mainly adsorbed via its acidic group on the BN nanocluster with adsorption energy about − 23.7 kcal/mol. In view of the high decrease of HOMO–LUMO energy gap (Eg) of the BN nanocluster after the adsorption process, it is expected that this process induces a significant increase in its electrical conductivity. Thus, the BN nanocluster is suggested as a potential sensor for CHC drug detection. We predicted that the BN cluster benefits from a short recovery time (~ 22.7 s) and high sensitivity (55.2% decrease in the Eg). Also, it is interesting that the BN nanocluster can be used as a sensor in the pristine form without needing to the functionalization, doping, decoration, etc. Finally, we showed that by increasing the percentage of Hartree–Fock exchange of the functional, the adsorption energy, and sensitivity are increased and decreased, respectively. Also, the sensitivity of the BN nanocluster is predicted to decrease in water solution.

An RP-LC method was developed and validated for separation and determination of seven antiviral drugs in their drug substances and drug products, using a BDS Hypersil C8 column at ambient temperature. The mobile phase was composed of 0.01 M KH2PO4 (pH 4):acetonitrile in gradient mode and the quantification was achieved at 245 nm for acyclovir, ganciclovir, penciclovir and valacyclovir hydrochloride, and at 220 nm for lamivudine, oseltamivir phosphate and ribavirin. Run time was 8 min, except for the oseltamivir-containing mixture where the run time was extended to 20 min. The validation of the method was assessed according to ICH guidelines. Linearity, accuracy and precision were satisfactory over the concentration ranges 3–100 µg mL−1 for acyclovir, ganciclovir and penciclovir; 5–100, 4–100, 7–120 and 5–120 µg mL−1 for valaciclovir HCl, lamivudine, oseltamivir phosphate and ribavirin, respectively. The developed method is suitable for the quality control and routine analysis of the cited drugs separately or in combinations. Moreover, the proposed method can be used for counterfeit drug detection. Also, simultaneous determination of lamivudine and penciclovir in spiked human plasma has been developed, using valaciclovir hydrochloride as an internal standard. Protein precipitation using perchloric acid solution was used for the extraction of the drugs from plasma. With modified chromatographic conditions, quantification was achieved at 254 nm. Validation of the method was performed according to European Medicines Agency guidelines with linearity over the range 0.056–4.0 and 0.14–10.0 μg mL−1 for lamivudine and penciclovir, respectively.

An electrochemical sensor for paracetamol is described that consists of a glassy carbon electrode (GCE) that was modified with the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) doped with MnO2 nanoflowers. The hydrothermally synthesized MnO2 nanoflowers possess a large surface area and can be doped into PEDOT through electrochemical deposition to form a conducting polymer nanocomposite. The nanoflowers are shown to be uniformly distributed within the nanocomposite as revealed by elemental mapping analysis. The nanocomposite displays excellent catalytic activity toward the electrochemical oxidation of paracetamol. The modified GCE, best operated at a working potential of around 0.37 V (vs. SCE) has a linear response in 0.06 to 435 μM paracetamol concentration range and a very low limit of detection (31 nM at a signal-to-noise ratio of 3). The sensor exhibits excellent reproducibility and stability, and satisfying accuracy for paracetamol detection in pharmaceutical samples.

Monitoring adherence to pre-exposure prophylaxis (PrEP) is part of the recommended package for PrEP prescribing, yet ongoing concerns about how to do so confidently are exacerbated by gross discrepancies in reported and actual use in clinical trials. We evaluated concordance between reports of recent PrEP dosing collected via neutral interviewing and drug quantitation in the iPrEx open-label extension, where participants (n = 1172) had the choice to receive or not receive PrEP. Self-report of recent dosing (at least one PrEP dose in the past 3-day) was the most common report (84 % of participants), and among these 83 % did have quantifiable levels of drug. The vast majority of those reporting no doses in the past 3-day (16 % of the sample) did not have quantifiable levels of drug (82 %). Predictors of over-report of dosing included younger age and lower educational attainment. Monitoring recent PrEP use through neutral interviewing may be a productive approach for clinicians to consider in implementation of real-world PrEP. Strategies to capture longer term or prevention-effective PrEP use, particularly for younger cohorts, are needed.

It is well known that under blue LED/laser illumination a class of synthetic conjugated polymers can create fluorescence, and after absorbing a certain class of explosive vapors the fluorescence will be quenched thus the explosives can be detected. The unsolved problems are how can we detect drug, TATP and nitro aromatic explosives with the same device, how can we distinguish different explosives and drugs, and how can we avoid false alarms; solving these problems are crucial for world security. We have developed a new synthetic conjugated polymer with single molecule layer and coated on porous silicon with large surface area to increase quenching signal at least one order, based on this new film a small handheld explosive detector with sensitivities of 0.1 pg for TNT and 0.1 ng for black gun powder are obtained. Many explosives and drugs (such as TNT, RDX, PETN, black gun powder, cocaine, etc.) have been tested, from their quenching curves and our data base we are able to distinguish them qualitatively and avoid false alarms. Therefore we believe our detector can be used not only for battle field but also for airports, government entrances and other security check points. Last year, after face to face competition, our device was selected as the only security detector for the G20 summit held in Hangzhou, China. Here, we will give our detailed designs to let readers develop detectors by themselves to counter terrorism in the world and save lives.

Present work elucidates the gas sensing and electrochemical sensing capabilities of sol–gel-derived nickel ferrite (NF) nanostructures based on the electrical and electrochemical properties. In current work, the choices of target species (acetone and acetaminophen) are strictly governed by their practical utility and concerning the safety measures. Acetone, the target analyte for gas sensing measurement is a common chemical used in varieties of application as well as provides an indirect way to monitor diabetes. The gas sensing experiments were performed within a homemade sensing chamber designed by our group. Acetone gas sensor (NF pellet sensor) response was monitored by tracking the change in resistance both in the presence and absence of acetone. At optimum operating temperature 300 °C, NF pellet sensor exhibits selective response for acetone in the presence of other common interfering gases like ethanol, benzene, and toluene. The electrochemical sensor fabricated to determine acetaminophen is prepared by coating NF onto the surface of pre-treated/cleaned pencil graphite electrode (NF-PGE). The common name of target analyte acetaminophen is paracetamol (PC), which is widespread worldwide as a well-known pain killer. Overdose of PC can cause renal failure even fatal diseases in children and demand accurate monitoring. Under optimal conditions NF-PGE shows a detection limit as low as 0.106 μM with selective detection ability towards acetaminophen in the presence of ascorbic acid (AA), which co-exists in our body. Use of cheap and abundant PGE instead of other electrodes (gold/Pt/glassy carbon electrode) can effectively reduce the cost barrier of such sensors. The obtained results elucidate an ample appeal of NF-sensors in real analytical applications viz. in environmental monitoring, pharmaceutical industry, drug detection, and health monitoring.

A system using energy dispersive X-ray diffraction has been tested to detect the presence of illicit drugs concealed within parcels typical of those which are imported into the UK via postal and courier services. The system was used to record diffraction data from calibration samples of diamorphine (heroin) and common cutting agents and a partial least squares regression model was established between diamorphine concentration and diffraction spectra. Parcels containing various crystalline and amorphous materials, including diamorphine, were then scanned to obtain multiple localised diffraction spectra and to form a hyperspectral image. The calibration model was used for the prediction of diamorphine concentration throughout the volume of parcels and enabled the presence and location of diamorphine to be determined from the visual inspection of concentration maps. This research demonstrates for the first time the potential of an EDXRD system to generate continuous hyperspectral images of real parcels from volume scanning in security applications and introduces the opportunity to explore hyperspectral image analysis in chemical and material identification. However, more work must be done to make the system ready for implementation in border control operations by bringing down the procedure time to operational requirements and by proving the system’s portability.

The aim of this study was to establish an ex vivo model for a faster optimisation of sample preparation procedures, for example matrix choice, in matrix-assisted laser desorption/ionisation (MALDI) drug imaging studies. The ionisation properties of four drugs, afatinib, erlotinib, irinotecan and pirfenidone, were determined in an ex vivo tissue experiment by spotting decreasing dilution series onto liver sections. Hereby, the drug signals were distinctly detectable using different matrix compounds, which allowed the selection of the optimal matrix for each drug. The analysis of afatinib and erlotinib yielded high drug signals with α-cyano-4-hydroxycinnamic acid matrix, whereas 2,3-dihydroxybenzoic acid was identified as optimal matrix for irinotecan and pirfenidone detection. Our method was validated by a MALDI drug imaging approach of in vivo treated mouse tissue resulting in corresponding findings, indicating the spotting method as an appropriate approach to determine the matrix of choice. The present study shows the accordance between the detection of ex vivo spotted drugs and in vivo administered drugs by MALDI-TOF and MALDI-FT-ICR imaging, which has not been demonstrated so far. Our data suggest the ex vivo tissue spotting method as an easy and reliable model to optimise MALDI imaging measurements and to predict drug detection in tissue sections derived from treated mice prior to the recruitment of laboratory animals, which helps to save animals, time and costs.

We present a rapid procedure for simultaneous extraction of a wide range of acidic and basic drugs from whole blood samples for reliable semi-quantitative NAGINATA drug screening by gas chromatography–mass spectrometry (GC–MS). To extract a wide range of drugs, the partition/extraction procedure used for the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, Safe) method was employed as the initial step. Various procedures were tested as the second step for the removal of whole blood impurities, including the use of primary secondary amine and C18 for the dispersive solid-phase extraction of the QuEChERS method, four kinds of silica-based C18 columns, alumina columns, and protein–lipid removal filter cartridges (Captiva ND Lipids). Subsequent GC–MS screening used the NAGINATA software with a constructed calibration-locking database for detection of acidic and basic drugs; drug detection ability, accuracy of tentative concentrations, and drug recoveries were examined and compared. We also examined the applicability of our established method in an actual forensic case. Our results showed that the number of drugs detectable at low concentrations was greatly increased by the use of the partition/extraction procedure of the QuEChERS method as the initial step and the protein–lipid removal filter cartridge as the second step. These combined steps provided notably clean extracts. Recoveries carefully measured with each reference standard were largely more than 60 %, and tentative concentrations obtained by the established screening method without reference standards were in the range of 48–310 % of the expected values for 65 acidic and basic drugs. Therefore, relatively reliable semi-quantitative values were obtained at the screening step without the need for each reference standard. We also experienced significant time savings for the extraction and in obtaining tentative concentrations at the screening step in an actual forensic case, indicating that the method is useful for rapid diagnosis of drug intoxication. Our proposed method should prove useful for semi-quantitative screening of a wide range of drugs and poisons in whole blood samples in clinical and forensic cases.

The chemical sensitivity of urine metabolomics analysis is greatly compromised due to the large amounts of inorganic salts in urine (NaCl, KCl), which are detrimental to analytical instrumentation, e.g. chromatographic columns or mass spectrometers. Traditional desalting approaches applied to urine pretreatment suffer from the chemical losses, which reduce the information depth of analysis. We aimed to test a simple approach for the simultaneous preconcentration and desalting of organic solutes in urine based on the collection of induced bursting bubble aerosols above the surface of urine samples. Bursting bubbles were generated at ambient conditions by feeding gas through an air diffuser at the bottom of diluted (200 times in ultrapure water) urine solution (50–500 mL). Collected aerosols were analyzed by the direct-infusion electrospray ionization mass spectrometry (ESI–MS). The simultaneous preconcentration (ca. 6–12 fold) and desalting (ca. six–tenfold) of organic solutes in urine was achieved by the bursting bubble sample pretreatment, which allowed ca. three-times higher number of identified urine metabolites by high-resolution MS analysis. No chemical losses due to bubbling were observed. The increased degree of MS data clustering was demonstrated on the principal component analysis of data sets from the urine of healthy people and from the urine people with renal insufficiency. At least ten times higher sensitivity of trace drug detection in urine was demonstrated for clenbuterol and salbutamol. Our results indicate the high versatility of bubble bursting as a simple pretreatment approach to enhance the chemical depth and sensitivity of urine analysis. The approach could be attractive for personalized medicine as well as for the diagnostics of renal disorders of different etiology (diabetic nephropathy, chronic renal failure, transplant-associated complications, oncological disorders). Urine desalting and preconcentration in bursting bubbles.

Application of near-infrared (NIR) measurements together with chemometric data processing is widely used for counterfeit drug detection. The most difficult counterfeits to detect are the "high quality fakes", which have the proper composition but are produced in violation of technological regulations by underground manufacturers. This study uses such forgeries and addresses important issues. The first is the possibility of applying the NIR/chemometric approach to the detection of injectable formulations of drugs (in this case dexamethasone), which are aqueous solutions with low concentration of active ingredients, directly in the closed ampoules. The second issue is the comparison of NIR/chemometric conclusions with detailed chemical analysis.

A forced degradation study of idebenone was conducted under conditions of UV irradiation, acid, basic and oxidative hydrolysis and in order to develop an isocratic stability-indicating LC-UV method for drug quantification in chitosan and N-carboxymethylchitosan nanoparticles obtained by spray drying. The drug was more labile to alkaline treatment than under the other forced degradation conditions. Idebenone and its degradation products were optimally resolved (resolution >4) on a Luna Phenomenex C18 column with mobile phase composed by methanol:water: (80:20% v/v) at a flow rate of 1.0 mL min−1, at 30 °C, using wavelength of 279 nm for drug detection. The method was linear, over a drug concentration range of 2 to 10 μg mL−1. The RSD% value of intra- and inter-day precision studies was

Background Tissue samples should be fixed and permanently stabilized as soon as possible ex-vivo to avoid variations in proteomic content. Tissues collected from studies involving infectious microorganisms, must face the additional challenge of pathogen inactivation before downstream proteomic analysis can be safely performed. Heat fixation using the Denator Stabilizor System (Gothenburg, Sweden) utilizes conductive heating, under a mild vacuum, to rapidly eliminate enzymatic degradation in tissue samples. Although many studies have reported on the ability of this method to stop proteolytic degradation and other sample changes immediately and permanently, pathogen inactivation has not been studied. Results We examined the ability of the heat fixation workflow to inactivate bacterial and viral pathogens and the suitability of this tissue for Matrix Assisted Laser Desorption Ionization mass spectrometry imaging (MALDI-MSI). Mice were infected with viral or bacterial pathogens representing two strains of Venezuelan Equine Encephalitis virus (VEEV) and two strains of Burkholderia. Additionally, a tissue mimetic model was employed using Escherichia, Klebsiella and Acinetobacter isolates. Infected tissue samples harvested from each animal or mimetic model were sectioned in half. One half was heat fixed and the other remained untreated. Lysates from each sample were checked for organism viability by performing plaque (infectivity) assays or plating on nutrient agar for colony forming unit (CFU) calculation. Untreated infected control tissue demonstrated the presence of each viable pathogen by positive plaque or colony formation, whereas heat fixation resulted in complete inactivation of both the viral and bacterial pathogens. MALDI-MSI images produced from heat fixed tissue were reflective of molecular distributions within brain, spleen and lung tissue structures. Conclusions We conclude that heat fixation inactivates viral and bacterial pathogens and is compatible with proteomic analysis by MALDI-MSI. This treatment will enable the use of infected tissue from studies performed in bio-safety level 3 laboratories with VEEV and Burkholderia to be safely used for proteomic, small molecule drug detection, and imaging mass spectrometry analysis.

A reversed-phase high-performance liquid chromatography method has been developed for the determination of proxodolol in the blood serum and tested in rabbits. The HPLC measurements were carried out using a Phenomenex (LUNA) C18 (5 μm) column eluted with acetonitrile-1 mM sodium pentylsulfonate (25: 75, v/v) mixture adjusted at pH 3.0 with phosphoric acid; eluent flow rate, 1 ml/min. The UV detector was tuned to 272 nm. Sample preparation: to 0.5 ml of blood serum in a 10-ml glass centrifuge tube is added 100 μl of 2.5 N NaOH and 4 ml chloroform; the mixture is shaken for 2 min and centrifuged at 3000 rpm for 10 minutes. The chloroform phase is separated and evaporated to dryness in a flow of nitrogen. The residue is dissolved in 100 μl of 1-mM sodium pentylsulfonate (pH 3); a 50 μl aliquot is introduced into the HPLC column. The proposed method is simple, rapid, sensitive, and has a good linearity. The average recovery of proxodolol is 80%. The drug detection limit is 0.015 μg/0.5 ml. The method is linear in the interval from 0.02 to 1.0 μg/0.5 ml with a correlation coefficient of 0.9996. The coefficient of variation is below 2% within a day (n = 5). The method was used for determining the parameters of proxodolol pharmacokinetics upon peroral administration in a dose of 40 mg in rabbits.

In recent years, drug analysis in keratinised matrices, such as hair and nails, has received considerable attention because of several advantages over drug testing methodologies employing body fluids, such as urine or serum. For example, keratinic matrices, such as finger- and toenails, can accumulate drugs during long term exposure. Drugs are incorporated into nails by a double mechanism: (i) deposition into the root of the growing nail via the blood flow in the nail matrix; and (ii) incorporation via the nail bed during growth from the lunula to the beginning of the free margin. Together, these account for a wide retrospective window of drug detection. Nails can provide a good forensic matrix for the detection of drugs of abuse. Indeed, the international literature has reported the use of nail analysis in postmortem detection of drugs of abuse, drug testing in the workplace and drug screening to detect prenatal exposure, even though further studies are needed for correct interpretation of the data obtained. Another application of drug analysis in nails consists of the possibility of detecting the presence of an antimycotic at the site of action during antifungal therapy for patients with onychomycosis. When available, this evidence has permitted drug treatment of a shorter duration and reduced toxicity. However, so far the potential of drug monitoring in nails still lacks harmonisation and validation of analytical methodologies and a better comprehension of the possible correlation between drug concentrations in the matrix and period of exposure.

Breath analysis could offer a non-invasive means of intravenous drug monitoring if robust correlations between drug concentrations in breath and blood can be established. In this study, propofol blood and breath concentrations were determined in an animal model under varying physiological conditions. Propofol concentrations in breath were determined by means of two independently calibrated analytical methods: continuous, real-time proton transfer reaction mass spectrometry (PTR-MS) and discontinuous solid-phase micro-extraction coupled with gas chromatography mass spectrometry (SPME-GC-MS). Blood concentrations were determined by means of SPME-GC-MS. Effects of changes in pulmonary blood flow resulting in a decreased cardiac output (CO) and effects of dobutamine administration resulting in an increased CO on propofol breath concentrations and on the correlation between propofol blood and breath concentrations were investigated in seven acutely instrumented pigs. Discontinuous propofol determination in breath by means of alveolar sampling and SPME-GC-MS showed good agreement (R2 = 0.959) with continuous alveolar real-time measurement by means of PTR-MS. In all investigated animals, increasing cardiac output led to a deterioration of the relationship between breath and blood propofol concentrations (R2 = 0.783 for gas chromatography-mass spectrometry and R2 = 0.795 for PTR-MS). Decreasing pulmonary blood flow and cardiac output through banding of the pulmonary artery did not significantly affect the relationship between propofol breath and blood concentrations (R2 > 0.90). Estimation of propofol blood concentrations from exhaled alveolar concentrations seems possible by means of different analytical methods even when cardiac output is decreased. Increases in cardiac output preclude prediction of blood propofol concentration from exhaled concentrations.

The real-time detection of cocaine in blood serum has been achieved using an aptamer-based electrochemical sensing device

At 800 pages, this is a doorstop of a book, containing contributions by 64 authors from 14 countries. So, first must be a word of congratulation to the editors for managing such a work that addresses their perceived need for an analytical text in clinical chemistry. This review cannot do justice to the 25 chapters, but it will try to give an overview of the book, dip into some of the offerings, and suggest its place in the literature of the field. The back-cover blurb suggests the book deals with the role of analytical chemistry in ‘‘fostering clinical research’’. So, the perspective is clearly on using analytical chemistry as a means to a number of ends. The branch of chemistry dealing with measurements in clinical science has often led to developments in instrumentation and stimulated wider metrological thinking in analytical chemistry. The need for safety of pharmaceuticals, adherence to regulations, production of timely results for clinicians and patients, and the need to measure ever tinier amounts of obscure compounds in more complex systems put a great task on clinical analytical chemists. It is not surprising that the first chapter in the section ‘‘Exploring Fundamentals’’ is titled ‘‘Good Clinical Practice Principles: Legal Background and Applicability’’. Here is detailed the major standards around Good Clinical Practice from ICH, WHO, and a number of EC directives. As a member of the Joint Committee for Guides on Metrology, Working Group 1 (the group responsible for the Guide to the Expression of Uncertainty in Measurement, GUM [1]), I was particularly interested in the chapter on uncertainty. The authors correctly use definitions from the International Vocabulary of Metrology, VIM [2], which puts the chapter on a sound metrological footing, unlike chapter 9.3 (Validation of Analytical Methods) which appears not have heard of VIM. The GUM is also referenced here, and the problem of ‘‘pre-analytical uncertainty’’ is raised. The chapter as a whole reads more of one addressing general quality issues than simply uncertainty, with sections on method validation, proficiency testing, and reference intervals. There is a tendency to make up quantities and symbols. SE here is short for systematic error, which most statisticians would read as ‘‘standard error’’. Two-letter acronyms abound when, in my opinion, the English words could appear certainly in the text. The space saved by ‘‘CM’’ over ‘‘control material’’ does not make up for the interruption to the reader’s flow, and the proper symbol in equations for standard deviation is s not SD. With all the extraneous, but interesting, material in this chapter, I am not sure whether a reader would be able to estimate a measurement uncertainty for a particular clinical measurement result. This chapter is a good example of the difference in outlook of, if I can call them thus, chemical analytical chemistry and clinical analytical chemistry, the former focusing on measurement, and the latter on process and the system as a whole. The last chapter in the Fundamentals section, on metal toxicology, seems out of place and perhaps should have been in the next section on Selected Applications, while chapter 8 on the role of analytical chemistry in the safety of drug therapy could perhaps have come into Fundamentals. The metals chapter could then have been put next to the chapter on molybdenum. In this section, the chapter of drug detection for antidoping controls caught my attention. This chapter is a nice essay on the state of play with reference to the major substances administered illicitly (EPO, steroids, growth hormones, and the plethora of agonists and antagonists). D. B. Hibbert (&) School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia e-mail: b.hibbert@unsw.edu.au

We would like to thank Drs. Zvosec and Smith for their compliments regarding our recent study of the effects of sodium oxybate and triazolam on different types of memory processes. We agree that these topics are important, in need of rigorous study, and have practical clinical implications. We also agree with Drs. Zvosec and Smith that there are potential differences between the number of forensic cases in which a drug can be detected and in which a drug was actually ingested. The difference between these two numbers is likely to be dependent on several factors, such as the dose of drug administered, the rate of drug metabolism, the storage of drug in body tissues, the ease of drug detection, and the availability of specific and sensitive forensic tests for the drug. For these reasons, the difference between the number of cases in which a drug is detected and the number of cases in which a drug is administered is likely to be larger for GHB compared to other drugs. However, even supposing that the detection of GHB is somewhat underestimated, the number of cases in which GHB is detected represents a small fraction of the number of cases in which ethanol is detected; a drug that is also metabolized relatively quickly (ElSohly and Salamone 1999; Slaughter 2000).

To investigate drug detection in samples of horse hair from the coat (on the neck), mane, and tail, three clenbuterol studies were conducted on a total of four horses. The analytical procedure consisted in acid hydrolysis of the hair, solid-phase extraction, and quantification by gas chromatography—tandem mass spectrometry in scan mode on an ion-trap instrument. The calibration was linear in the range 4 to 60 pg mg−1. The limit of detection was 1 pg mg−1. The method enabled retrospective analysis-measurement of clenbuterol in the tail was possible for up to 13 months after the last administration of drug.

The literature on the effects of prenatal cocaine exposure on child outcome is inconclusive. Thus, we developed a computerized database of the scientific literature to summarize the literature. The method includes a Medline and Psychlit search, review of each article for eligibility based on predefined inclusion criteria, and abstraction of information from each article coded and entered into the database. Defined variables included characteristics of the study or behavioral outcomes. Of 133 studies published between 1985- June 1997, 101 (76%) met inclusion criteria. Of the 101 studies only 12% reported that cocaine was the only drug involved showing that the problem is one of polydrug abuse. Most studies (83%) used multiple methods of drug detection(urine and self-report) with only 4 studies using meconium. Control for SES was reported in 53% and control for medical factors (e.g. gestational age) was reported in 59%. Little is known about long term follow-up: 77% studied infancy, 13% early childhood and 10% school age children. Surprisingly, examiner blindness was only reported in 62% of the studies. In the 101 studies, a total of 1507 behavioral effects were reported. There were 476(32%) adverse cocaine effects. Using meta-analysis techniques, the mean difference in IQ scores between exposed and controls for the 5 studies in which this was available was 3.26 points. However, even this small difference will shift the normal distribution curve resulting in 3.75% rather than 2.28% who will score .75 SD). The IQ difference is an effect size of.27 SD. Language outcome studies show a mean effect size of.53 SD for receptive and.59 SD for expressive language, resulting in a 3.1 (26,550) and a 3.4 (29,737) fold increase in number of children affected, respectively. The yearly costs for special education services would be $168 million for receptive and $188 million for expressive language delays. The literature shows most affects are small to medium. However, in 35% of the studies, the sample size is 80) to detect small effects. However, even small effects can affect large numbers of children resulting in large expenditures for special education services.

We have shown (Dev Pharm Ther 1:163, 1980) in morphine addicted fetal monkeys that the tissue concentration of morphine was highest in their intestines due to bile secretion or swallowed fetal urine. To test the corollary hypothesis that the stools from infants of drug dependent mothers (IDDM) will contain the drugs which the fetus has been exposed to, in utero, we collected stools (meconium) during the first 5 days from 10 IDDMs and 2 control infants and tested them for the metabolites of heroin (morphine), cocaine (benzoylecgonine), and cannabis (Δ 9 tetrahydrocannabinol or THC), three commonly abused drugs. In addition, we addicted a pregnant Sprague-Dawley rat by the daily subcutaneous injections of morphine sulfate (10-20 mgs/kg bid) from the 8th to the 21st day of gestation. Soon after birth, the rat pups were sacrificed and their intestines were collected for morphine analysis. The drug metabolites were extracted in appropriate solvents and quantitated by radioimmunoassay. The control stools were used for background correction. RESULTS: Four of the 10 IDDM stools contained morphine (range = 0.24-22.7 μg/gm stool, mean = 5.42) and 3 had cocaine metabolites (range = 0.24-0.67 μg/gm stool, mean = 0.42) up to the 2nd day of sampling. Five of 5 stools tested contained Δ 9 THC (range = 0.023-1.082 μg/gm stool, mean = 0.37) up to the 5th day sample. In the 9 rat pups, their intestinal contents collectively contained 1.65 μg of morphine or 0.18 μg morphine per pup. SIGNIFICANCE: This study shows that the stool (intestinal content) is a repository of the drugs which the fetus has been exposed to, in utero, and their detection may provide a unique insight into the drug exposure of the fetus throughout gestation. Likewise, since the complete evacuation of meconium occurs slowly, drug detection for diagnostic purposes in infants, is feasible even in late sampling.