3D-printed portable device for illicit drug identification based on smartphone-imaging and artificial neural networks.

In this manuscript, a 3D-printed analytical device has been successfully developed to classify illicit drugs using smartphone-based colorimetry. Representative compounds of different families, including cocaine, 3,4-methylenedioxy-methamphetamine (MDMA), amphetamine and cathinone derivatives, pyrrolidine cathinones, and 3,4-methylenedioxy cathinones, have been analyzed and classified after appropriate reaction with Marquis, gallic acid, sulfuric acid, Simon and Scott reagents. A picture of the colored products was acquired using a smartphone, and the corrected RGB values were used as input data in the chemometric treatment. ANN using two active layers of nodes (6 nodes in layer 1 and 2 nodes in layer 2) with a sigmoidal transfer function and a minimum strict threshold of 0.50 identified illicit drug samples with a sensitivity higher than 83.4 % and a specificity of 100 % with limits of detection in the microgram range. The 3D printed device can operate connected to a rechargeable lithium-ion cell portable battery, is inexpensive, and requires minimal training. The analytical device has been able to discriminate the analyzed psychoactive substances from cutting and mixing agents, being a useful tool for law enforcement agents to use as a screening method.

Determination of synthetic cannabinoids in oral fluids by liquid chromatography with fluorescence detection after solid-phase extraction.

Synthetic cannabinoids are one of the most consumed new psychoactive substances, being absolutely necessary the development of analytical methodologies for the determination of these substances in biological fluids. In this study, a liquid chromatography with fluorescence detection (LC-FD) method has been developed for the analysis of 8 synthetic cannabinoids in oral fluids. The method has been validated in terms of linearity, precision and extraction recoveries, giving limits of detection as low as 0.7 µg L-1, and limits of quantification of 2.6 µg L-1. Different silica and polymeric commercial solid sorbents such as C18, Supel-Select HLB, EB2 ExtrabondⓇ and SampliQ-OPT were tested, concluding that Supel-Select HLB provided quantitative recoveries for the extraction of synthetic cannabinoids in oral fluids.•Analysis of synthetic cannabinoids in oral fluids.•Analytical procedure based on liquid chromatography with fluorescence detection.•Sample treatment based on solid phase extraction with HLB cartridges.

Paper-based monolith extraction of psychoactive substances from biological fluids.

A monolith of poly(methacrylic acid-co-ethylene glycol dimethacrylate) has been immobilised to a nitrocellulose strip by radical photopolymerisation to be used in the extraction of psychoactive substances in biological fluids. Codeine, methylone, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, butylone, norketamine, ketamine, heroin, cocaine, lysergic acid diethylamide and fentanyl were employed as model drugs and final extracts were analysed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Polymerisation parameters were adjusted in order to obtain a stable and homogeneous layer of monolith onto the nitrocellulose strip. The resulting sorptive phase was characterized by Fourier-transform infrared spectroscopy and scanning electron microscopy. Extraction conditions were investigated by the evaluation of sample pH, extraction and desorption times and desorption solvent volume, providing enrichment factor values ranging from 5.3 to 39.9. The proposed methodology provided limit of quantification values from 0.013 µg L-1 for methylone to 0.057 µg L-1 for amphetamine, and recoveries from 64 to 120%. Urine and serum certified reference materials were employed in the validation of the proposed methodology, providing results statistically comparable. The developed approach is simple and straightforward for the determination of psychoactive substances in urine and serum samples.

Molecularly imprinted polymer-based device for field collection of oral fluid samples for cocaine identification.

In this paper, a low-cost, rapid, easy, and potentially portable tool for the identification of cocaine and its semi-quantitative determination in oral fluid has been proposed. A field collection device has been designed, based on a cotton pad with an indicator and a molecularly imprinted polymer (MIP) sorbent, to selective retain cocaine from oral fluid components. After sample collection, cocaine is transferred by using phosphate buffer to the MIP and then eluted with 2-propanol. The obtained extract is analysed by ion mobility spectrometry (IMS), providing a cut-off value of 20 µg L-1 that identifies 100 % true-positive and 95 % true-negative samples. The MIP-IMS procedure has been validated by the analysis of oral fluid samples, collected from cocaine users at recreation environments, by comparing the results with lateral flow immunoassay and chromatographic reference methods. Thus, the proposed methodology allows a simple and fast cocaine identification that can be carried out in field by non-specialized personnel, such as health personnel, law enforcement bodies, and customs staff.

Tuning the selectivity of molecularly imprinted polymer extraction of arylcyclohexylamines: From class-selective to specific.

A molecularly imprinted polymer (MIP) has been prepared in presence of 3-hydroxy phencyclidine (3-OH PCP) as template by bulk polymerization using N,N-dimethylformamide, as porogenic solvent, for the selective solid-phase extraction (SPE) of arylcyclohexylamines from oral fluids. Experimental variables of the extraction procedure have been studied in order to increase both, extraction recovery of 3-OH PCP, used as model analyte, and imprinting factor. By modifying the composition of the washing solvent, the selectivity of the MIP extraction procedure can be tuned, moving from an arylcyclohexylamine selective method to a 3-OH PCP specific method. The applicability of the synthesized MIP was evaluated by the analysis of oral fluids spiked with 3-OH PCP at different concentration levels, extracted using both recommended SPE procedures and analyzed by ion mobility spectrometry. Recovery values ranging from 70 to 101% and a limit of detection of 15 µg L-1 were obtained.

Development of pipette tip-based poly(methacrylic acid-co-ethylene glycol dimethacrylate) monolith for the extraction of drugs of abuse from oral fluid samples.

In this work, a monolithic polymer based on poly(methacrylic acid-co-ethylene glycol dimethacrylate) (MAA-co-EDMA) was prepared inside 200 µL pipette tips for the extraction of drug of abuse from oral fluid samples. After an appropriate surface tip modification, several polymerization mixtures with different monomer/cross-linker ratios, and percentage of porogen were studied. The most appropriate monolith to easily flow organic solvents and oral fluid samples was prepared with a MAA/EDMA ratio of 8:92 wt/wt and dodecanol containing 10 wt% toluene, as porogenic solvent. Parameters affecting the extraction procedure were evaluated and the monolith was characterized in terms of binding capacity, reusability, and precision, using α-pyrrolidinovalerophenone as model compound. Cocaine, diazepam, methamphetamine and 20 new psychoactive substances were determined in oral fluids, using the synthesized poly(MAA-co-EDMA) monolith in-tip on an eight-channel micropipette extraction and ultra-high performance liquid chromatography tandem mass spectrometry. Appropriate recoveries were obtained, ranging from 64 to 115%, with limit of detection values from 0.03 to 0.6 µg L-1, and a high precision with relative standard deviation values lower than 10% for all the evaluated drugs.

Development of a molecularly imprinted monolithic polymer disk for agitation-extraction of ecgonine methyl ester from environmental water.

In this study, a new extraction approach based on rotating molecularly imprinted polymer (MIP) disks was developed. The preparation procedure of MIP-disk is simple. Firstly, in order to immobilize MIP onto the surface of polytetrafluoroethylene (PTFE) disk, previous modification and vinylization steps of this fluoropolymer were conducted. Then, MIP synthesis was done by in situ polymerization. The resulting MIP was characterized by Fourier-transform infrared spectroscopy and scanning electron microscopy. Afterwards, two ring magnets were placed in the sides of the MIP-disk to integrate the stirring and preconcentration of sample in just one step. To demonstrate the feasibility of this novel extraction system, the selective extraction of ecgonine methyl ester (EME) from water samples was performed. Extraction conditions were also evaluated and the extracts were analyzed by ion mobility spectrometry and by ultrahigh performance liquid chromatography-tandem mass spectrometry, allowing limits of detection of 13 and 75 ng L-1, respectively. Field surface water and wastewater were analyzed using the proposed methodology, being a good alternative for the fast and potentially portable methodology for in-field screening analysis.

Ion mobility spectrometry and high resolution mass-spectrometry as methodologies for rapid identification of the last generation of new psychoactive substances.

A new drug trafficking trend has been observed in the last years by the introduction in the black market of new psychoactive substances (NPS) in order to difficult competent authority controls. In this study, ion mobility spectrometry (IMS) and high-resolution mass-spectrometry (HRMS) were proposed as vanguard and rearguard methodologies for the rapid identification of the last generation of NPS in seizures. The combined use of IMS and HRMS has been evaluated through the analysis of 24 NPS seized from 2016 to 2018 in Valencia (Spain) to demonstrate the utility of this approach. The characteristic reduced mobility (K0) values for seized NPS were determined and mass-mobility relationships were proposed and evaluated for the main NPS families: amphetamine and cathinone derivatives, and synthetic cannabinoids. IMS did not allow a unequivocal identification by itself; so, HRMS analysis was employed as rearguard confirmation methodology for the right identification of NPS. Thus, the combined use of IMS and HRMS can be considered as promising alternative for the rapid screening and identification of NPS in seizures.

Trace analysis by ion mobility spectrometry: From conventional to smart sample preconcentration methods. A review.

Ion mobility spectrometry (IMS) is a rapid and high sensitive technique widely used in security and forensic areas. However, a lack of selectivity is usually observed in the analysis of complex samples due to the scarce resolution of the technique. The literature concerning the use of conventional and novel smart materials in the pretreatment and preconcentration of samples previous to IMS determinations has been critically reviewed. The most relevant strategies to enhance selectivity and sensitivity of IMS determinations have been widely discussed, based in the use of smart materials, as immunosorbents, aptamers, molecularly imprinted polymers (MIPs), ionic liquids (ILs) and nanomaterial. The observed trend is focused on the development of IMS analytical methods in combination of selective sample treatments in order to achieve quick, reliable, sensitive, and selective methods for the analysis of complex samples such as biological fluids, food, or environmental samples.

Ion mobility spectrometry as a fast analytical tool in benzalkonium chloride homologs determination.

A novel procedure is proposed for the determination by ion mobility spectrometry (IMS) of C12, C14 and C16 benzalkonium chloride (BAC) homologs. The proposed method requires minimum sample treatment and the measurement was made in less than one minute. A high sensitivity was obtained for BAC determination by IMS with limit of detection values from 37 to 69µgL-1. Accuracy of the proposed methodology was evaluated through the analysis of aqueous and alcoholic samples spiked with BAC at concentration levels from 0.002% to 20% (w/v), providing recovery values from 91% to 104%. BAC was determined in sanitary alcohols, nasal sprays, postharvest products, algaecides, and treated swimming pool water. Results obtained by the proposed IMS methodology were statistically comparable to those provided by a liquid chromatography-ultraviolet (LC-UV) reference methodology. The Green Certificate evaluation of the proposed IMS methodology provided 91 score points in the Eco-Scale as compared with 77 for LC-UV method.

Cocaine abuse determination by ion mobility spectrometry using molecular imprinting.

A cocaine-based molecular imprinted polymer (MIP) has been produced by bulk polymerization and employed as selective solid-phase extraction support for the determination of cocaine in saliva samples by ion mobility spectrometry (IMS). The most appropriate conditions for washing and elution of cocaine from MIPs were studied and MIPs were characterized in terms of analyte binding capacity, reusability in water and saliva analysis, imprinting factor and selectivity were established and compared with non-imprinted polymers. The proposed MIP-IMS method provided a LOD of 18µgL-1 and quantitative recoveries for blank saliva samples spiked from 75 to 500µgL-1 cocaine. Oral fluid samples were collected from cocaine consumers and analysed by the proposed MIP-IMS methodology. Results, ranging from below the LOD to 51±2mgL-1, were statistically comparable to those obtained by a confirmatory gas chromatography-mass spectrometry method. Moreover, results were compared to a qualitative lateral flow immunoassay procedure providing similar classification of the samples. Thus, MIP-IMS can be considered an useful alternative that provided fast, selective and sensitive results with a cost affordable instrumentation that does not require skilled operators.

Indoor and outdoor determination of pesticides in air by ion mobility spectrometry.

The use of ion mobility spectrometry (IMS) has been evaluated as analytical methodology to detect and evaluate the occupational exposure to pesticides. The developed IMS methodology was used, in positive and negative modes, to determine the presence of pesticides in air and to evaluate possible inhalation exposures of workers and users based on active sampling on Teflon membranes and direct thermal desorption IMS. The negative IMS mode was used to determine bensulfuron, clorpyrifos, diniconazole, diuron, flutolanil and imidacloprid, while the positive mode was employed to evaluate formetanate, metalaxyl, metamitrone, metribuzin, paclobutrazol and pirimicarb. The IMS measurements provided limits of detection from 8pg to 600pg. Indoor air samples, from phytosanitary plants, and outdoor samples, obtained from pesticide treatments in a local farm, were analysed providing pesticide air concentrations in the range of 0.04 to>0.25mgm-3. Occupational exposure of workers and pesticide users were evaluated and compared with values recommended by the authorities, providing useful information to improve the prevention programs in the phytosanitary field.

Passive exposure to nicotine from e-cigarettes.

A procedure based on the use of ion mobility spectrometry (IMS), after liquid-liquid microextraction (LLME), has been successfully employed for the determination of passive exposure to nicotine from cigarette and e-cigarette smoking. Nicotine has been determined in exhaled breath and oral fluids of both, active and passive smokers. The aforementioned studies, made in closed environments, evidenced that the exhaled breath after conventional blend cigarette smoke provides nicotine levels of the order of 220 ng per puff, in the case of experienced smokers, being exhaled only 32 ng in the case of e-cigarettes. On the other hand, the nicotine amount in oral fluids of passive vapers was between 8 and 14 µg L(-1) lower than the average value of 38±14 µg L(-1) found for passive smokers of rolling tobacco and clearly lower than the 79±36 µg L(-1) obtained from passive smokers of classical yellow blend. This study was also placed in the frame of the verification of the e-cigarettes composition.

Green near-infrared determination of copper and mancozeb in pesticide formulations.

A green analytical procedure has been successfully developed for the simultaneous determination of copper and mancozeb in phytosanitary products. The method is based on different direct measurements of diffuse reflectance near-infrared (DR-NIR) spectra. Accuracy of the method has been evaluated by comparison of the obtained copper and mancozeb concentrations with those provided by reference methodologies based on titrimetric procedures. The average relative prediction error was 0.7 and 1.6 % for copper and mancozeb, respectively. The evaluation of the greenness of the DR-NIR procedure provided 100 points, which is the maximum value in the Green Certificate ranking, because of the absence of consumed reagents and waste generation and energy consumption lower than 0.1 kWh.

A new approach to determine the homogeneity in hyperspectral imaging considering the particle size.

Determining homogeneity of a mixture using hyperspectral-imaging (HSI) techniques is at this moment an interesting research subject in pharmaceutical industry. A new methodology based in the macropixel analysis technique for the homogeneity assessment in powder blend mixtures has been developed. The appropriate selection of the macropixel size for evaluation of the homogeneity is a topic under discussion. We propose that the macropixel size selection would be based in a statistical criterion called "representative sample size" criterion. Moreover, it has been demonstrated that the macropixel size should be a function of the particle size and, thus, the particle size has been included in the formula to calculate the macropixel size. The proposed equations allow to accurately calculate the homogeneity index (H% Poole). By means of using simulated chemical images, a relationship between the H% Poole index and the controlled homogeneity was established. The method has been applied to determine the homogeneity of binary and ternary powder blends mixtures of different pharmaceuticals discriminating between homogeneous and non-homogeneous samples.

Ion mobility spectrometry for the simultaneous determination of diacetyl midecamycin and detergents in cleaning validation.

In the present paper, we have developed two different approaches based on ion mobility spectrometry (IMS) for the cleaning validation of diacetyl midecamycin in the surfaces of manufacture equipment: a semi-quantitative approach based on the use of a sample wand and a quantitative procedure based on the swab test. The simultaneous determination of the active pharmaceutical ingredient and cleaning agents has been performed without important effects of ionization suppression upon the analysis of swabs containing multiple components. Sensitivity, in the ng range, and appropriate selectivity ratify IMS as a serious alternative, a fast and serious alternative in cleaning validation. Other advantage imply its potential for at-line use to perform a semi-quantitative procedure using a sample wand which allows Teflon membranes, swabbed onto the stainless steel surfaces, to be introduced directly into the instrument with no dilution or extraction.

Spray nebulization for sample introduction in ion mobility spectrometry.

A new sample introduction system based on spray nebulization has been successfully developed to perform direct analysis of liquid samples by IMS. The system comprises a concentric nebulizer that generates a spray plume which is introduced in the ionization region of the IMS instrument through a temperature controlled transfer line. This system avoids previous problems of direct injection of liquid samples and maintains the countercurrent flow of inert gas necessary for the operation of the IMS instrument. Evaluation of the qualitative and quantitative capabilities of the methodology has been performed after a carefully study of the main variables affecting the spray nebulization and the transport of the analyte molecules through the transfer line. To demonstrate the usefulness of the new sample introduction system, direct analysis of drugs and drug metabolites in saliva or urine samples have been performed, obtaining accurate, reliable and sensitive results. Moreover, analytes with physico-chemical properties that limited the capability of thermal desorption as sample introduction method such as amino acids can be analyzed by using the spray nebulization methodology.

Ion mobility spectrometry: a comprehensive and versatile tool for occupational pharmaceutical exposure assessment.

The qualitative and quantitative capabilities of ion mobility spectrometry (IMS) as a comprehensive and powerful tool in workplace air monitoring have been demonstrated on the example of a Spanish pharmaceutical company. The developed IMS based procedure is capable of detecting and determining in air samples the active pharmaceutical ingredients (APIs) manipulated and/or produced in this pharmaceutical industry. Sensitivity, in the ng-pg range, selectivity, possibly to provide results in near real time, and reduction of analysis costs are the most important properties that ratify IMS as a serious alternative in occupational exposure assessment. The possibility of false positives by drift time interferences and false negatives by competitive ionization and also desorption process interferences has been deeply evaluated. Moreover, chemometric strategies based on self-modeling curve resolution (SMCR) have been applied to obtain qualitative and quantitative individual component information from overlapped peaks. The IMS procedure has been successfully applied to evaluate the concentration of APIs (nimesulide, dexketoprofen, deflazacort) handled by the pharmaceutical company employees in the making of tablets and granulates, and control measures have been suggested in accordance.

Ion mobility spectrometry as a high-throughput analytical tool in occupational pyrethroid exposure.

The capabilities of ion mobility spectrometry (IMS) as a high throughput and green analytical tool in the occupational health and safety control, using pyrethroids as models has been evidenced. The method used for dermal and inhalation exposure assessment is based on the passive pyrethroid sampling using Teflon membranes, direct thermal extraction of the pyrethroids, and measurement of the vaporized analytes by IMS without reagent and solvent consumption. The IMS signatures of the studied synthetic pyrethroids under atmospheric pressure chemical ionization by investigating the formed negative ion products have been obtained. The main advantages of the proposed procedure are related to the obtained limits of detection, ranging from 0.08 to 5 ng, the simplicity of measurement, the lack of sample treatment, and therefore, solvent consumption and waste generation, and finally, the speed of analysis.

Pros and cons of benzodiazepines screening in human saliva by ion mobility spectrometry.

The usefulness of ion mobility spectrometry as a screening methodology for the on-site benzodiazepine analysis in saliva samples has been critically evaluated. The procedure involved the injection of clear supernatant extracts after centrifugation and provided limit of detection values ranging from 2.0 to 18 µg L(-1), and a precision, expressed as relative standard deviation, from 2.9% to 16%, depending on the different benzodiazepines studied. Those values are appropriate for their positive identification in saliva samples in which benzodiazepine concentration, after a chronic or acute dose, is in the range of 2-30 µg L(-1). Problems related with overlapped benzodiazepine signals have been successfully overcome by application of multivariate curve resolution, which is a helpful tool to improve the resolution of the technique, without sacrificing the method simplicity and frequency of analysis. The possibility of false positives caused by the presence of interferents with the same drift time as the benzodiazepines and the possibility of false negatives due to the presence of interferents by competitive ionization have been critically evaluated. The satisfactory results obtained for the analysis of real saliva samples after an acute dose of diazepam through sublingual and oral intakes confirm the capability of the technique to be used as a screening methodology in the analysis of benzodiazepines in oral fluids.