Fabrication of an Optoplasmonic Raft with Improved SERS Performance Detecting Methamphetamine through Bubble Enrichment.

In this work, a novel raft-like structure that combines noble metal nanoparticles (NPs) with an interconnected layer of hemispherical dielectric shell was fabricated and characterized. It was discovered that this hybrid material can enhance the optoplasmonic interaction between plasmonic and dielectric components, thereby improving the sensing performance in surface-enhanced Raman spectroscopy (SERS). Varied geometric parameters of the fabricated optoplasmonic raft, including the inner diameter and thickness of the dielectric shell, were attempted and analyzed through numerical simulation and experimental SERS measurements. With particular size, thickness, and incident orientation, the silica shell focuses the incident optical flow into the deposited silver NPs, undergoing similar near-field focusing behavior in comparison with other optoplasmonic entities. This optoplasmonic raft floating on the water surface is able to harvest the target molecules effectively through bubble enrichment, which rapidly captures and concentrates analytes from the aqueous phase. With a limited sampling time, the sensing performance of the developed optoplasmonic raft is improved by applying the optimized parameters involved in bubble enrichment. The substrates and corresponding enrichment method were implemented in the detection of methamphetamine (METH), achieving a limit of detection (LOD) down to 0.035 nM. As for practical onsite detection, the developed substrate and bubbling strategy were applied in an assembled set, employing a portable Raman spectrometer and an air pump. This set is able to detect METH dissolved in regular commercial beer, which is quite competent in the investigation of drug abuse.

Identification of novel 3-aryl-1-aminoisoquinolines-based KRASG12C inhibitors: Rational drug design and expedient construction by CH functionalization/annulation.

Developing a synthetic methodology to expediently construct a specific drug scaffold with the desired biological activity remains challenging. Herein, we describe a work on rational application of a synthetic methodology in the synthesis of KRASG12C inhibitors. Novel KRASG12C inhibitors were initially designed with 1-amino-3-aryl isoquinoline scaffold using structure-based drug design strategy. A ruthenium-catalyzed direct monoCH functionalization/annulation cascade reaction of amidines and sulfoxonium ylides was then developed with high versatility of substrates and good tolerance for polar functional groups. By using this reaction, the target compounds 1-amino-3-aryl isoquinolines were facilely prepared. Further in vitro tests led to identification of two novel lead compounds with KRASG12C inhibitory activity.

A comprehensive LC-MS/MS method for simultaneous analysis of 65 synthetic cannabinoids in human hair samples and application to forensic investigations.

Synthetic cannabinoids (SCs) represent a diverse class of new psychoactive substances characterized by extensive substance variety and severe abuse implications. The current situation of synthetic cannabinoid abuse in China is getting worse, with an increasing number of SC variants emerging. Therefore, it is imperative to improve synthetic cannabinoid detecting methods to align with the prevalent abuse situation in the region. In this study, a reliable and validated liquid chromatography-tandem mass spectrometry method was developed for the qualitative and quantitative analysis of 65 SC analogues in human hair samples. The validation results demonstrated satisfactory linearity (r ≥ 0.99) within the range of 25-2500 pg/mg for each SC analogue. The method exhibited limits of detection ranging from 10 to 15 pg/mg and limits of quantification ranging from 25 to 40 pg/mg. The relative standard deviations of intra-day precision and inter-day precision were below 15 %. Furthermore, negligible matrix effects were observed, with recovery rates ranging from 85.70 % to 119.43 %. Analysis of abuser demographics revealed that the primary group engaged in SC analogue abuse consisted of adolescents, predominantly males, accounting for 79.5 % of cases. Among the suspected individuals, ADB-BUTINACA and MDMB-4en-PINACA were the most frequently detected substances. The present study develops a highly sensitive analytical method and provides a comprehensive overview of the prevalence of SC abuse in the eastern region of China.

Electrochemical Oxidative C-H Amination through a Ritter-Type Reaction.

A straightforward strategy for direct benzylic C-H bond amination via an electrochemical Ritter-type reaction is developed. The reaction demonstrates simpler and milder reaction conditions over the existing methods without extra mediator. Moderate to excellent yields up to 94% of the desired amide products were obtained with a broad substrate scope. The removal of the Ac group by a simple step can afford NH-free benzylic amines, providing a suitable approach for the late-stage functionalization of bioactive molecules.

Surface-enhanced Raman imaging through sprayed probes for the application in chemical visualization of methamphetamine within fingerprints.

For fingerprint-involved forensic investigations, cyanoacrylates and inorganic nanophosphors are mostly used for fingerprint visualization. However, methods to simultaneously report fingerprint images and the corresponding specific chemical information have yet to be realized. In this work, chemical visualization of the analytes in fingerprints is achieved through surface-enhanced Raman spectroscopy (SERS) measurements with the aid of spray-dispersed gold nanorods (AuNRs). The optimal coverage of AuNRs was studied by theoretical simulations and experimental operations. A rapid sampling of fingerprints with the chemical of interest was developed by tuning the spray parameters. In particular, the SERS imaging of methamphetamine in fingerprint latent was attempted by addressing the SERS spectral features of methamphetamine. This chemical visualization method reflects both the graphical and chemical characteristics of fingerprints in a single batch measurement, in which methamphetamine can be detected and mapped at the concentration of 10-5 M. The data processing approach was also modified by employing relevant logical judgments. The improved SERS images with sharpened patterns of fingerprints were obtained by involving the scored multi-peak judgments.

Iron-Catalyzed C-C Bond Cleavage of Oximes for Direct Coupling of Benzothiazole in Water.

An Fe-catalyzed coupling reaction between oxime ester and benzothiazole is described, which involves C-C bond cleavage of oxime ester via a single-electron transfer process. This iron catalytic system performed in water under mild reaction conditions offers a streamlined strategy to the construction of alkyl nitrile substituted benzothiazole derivatives. Application of this strategy for the synthesis of some key important compounds including 4-heterocyclic-3-arylbutanoic acid is also reported.

Establishment and application of a screening method for 354 organic toxicants in blood and urine with high-performance liquid chromatography-high-resolution orbitrap mass spectrometry.

A rapid and sensitive high-performance liquid chromatography-high-resolution orbitrap mass spectrometry method was developed for the simultaneous screening of 354 organic poisons and metabolites in blood and urine, including drugs, medications, pesticides, rodenticides, veterinary drugs, alkaloids, and mycotoxins with a multi-toxicant chromatography-mass spectrometry information library. The method and library showed good prospects in clinical poisoning screening and forensic toxicological identification. Blood and urine samples were extracted successively with ethyl acetate in acidic and alkaline conditions; then, the extract was blown to nearly dry by nitrogen gas and redissolved with methanol-aqueous solution (v:v, 50:50), and the dissolved solution was analyzed by LC-MS/MS after filtering. Precursor ions' m/z was set for identification, retention time, fragment ions, and isotopic pattern which were used for confirmation. No interference peaks were found in the blank samples, showing good specificity. The LODs of toxicants in urine and blood were 1.00×10-3-50.0 ng/mL and 2.07×10-3-50.0 ng/mL, respectively, while the LOQs were 3.30×10-3-1.67×102 ng/mL and 6.91×10-3-1.67×102 ng/mL. The intra-day precision and inter-day precision of urine samples were 2.31-9.13% and 4.75-12.3%, respectively, which were 1.92-10.8% and 2.01-12.1% in blood samples. The established method was applied to analyze 9 cases of clinical poisoning patients, and bromadiolone, carbofuran, and amanitins were detected, respectively. A total of 382 biospecimens from drug abusers were analyzed with the proposed method, which indicated that some drugs were detected in 62 cases, mainly including methamphetamine, heroin, and MDMA. The results were consistent with the information from traditional liquid chromatography-triple quadrupole mass spectrometry.

Consumption of common illicit drugs in twenty-one cities in southwest China through wastewater analysis.

Wastewater-based epidemiology (WBE) was applied to estimate illicit drugs consumption at a provincial scale in southwest China. A large-scale wastewater sampling campaign was carried out from October to November in 2021 in 156 different wastewater treatment plants (WWTPs). Two 24-h composite influent wastewater samples were collected in each WWTP. Concentrations of 11 illicit drugs or their metabolites were determined using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Benzoylecgonine, cocaine, 6-monoacetylmorphine, norketamine, 3,4-methylenedioxymethamphetamine (MDMA), and MDA were not detected in any of the wastewater samples. Methamphetamine and morphine were detected in >84% of samples, while ketamine was found in about 6% of the samples. The city-specific population-weighted consumption of methamphetamine and ketamine were in the range of 0.6-49.7 and N.D.-7.0 mg 1000 inh-1 day-1, respectively, with provincial population-weighted values of 22.6 and 2.4 mg 1000 inh-1 day-1 in southwest China. The city-specific load of morphine varied from 3.2 to 10.2 mg 1000 inh-1 day-1, with provincial population-weighted load of 6.7 mg 1000 inh-1 day-1. Taking into account therapeutic use of morphine and codeine, the provincial heroin consumption was estimated to be 10.3 mg 1000 inh-1 day-1, ranging from 1.7 to 18.5 mg 1000 inh-1 day-1 in 21 cities. Overall, the patterns of illicit drugs use were similar across southwest China, with high prevalence of methamphetamine and heroin, but relatively low use of ketamine. These findings could provide accurate drugs consumption information for timely identifying potential hotspots of illicit drugs use in southwest China.

[The Screening Approaches for 34 Common Drugs and Metabolites in Biological Samples by Liquid Chromatography Orbital Trap Mass Spectrometry].

Objective: To establish a high-performance liquid chromatography orbital trap mass spectrometry (HPLC-Obitrap MS) method for screening 34 common drugs and metabolites in biological samples. Methods: The target analytes in urine and blood samples were extracted with ethyl acetate, concentrated by nitrogen blowing and redissolved. The hair samples were washed with water and acetone, dried and cut into bits of about 1 mm, and then crushed in a freezing grinder. The analytes were extracted with methanol, and after filtration, the filtrate was used for instrumental analysis. Hypersil Gold PFP (2.1 mm×100 mm, 3 µm) column was used for chromatographic separation. Methanol and 5 mmol/L ammonium acetate solution were used as mobile phase with gradient elution at a flow rate of 400 µL/min. Mass spectrometry was done by electrospray positive and negative ion alternation mode. The data were collected using Full MS and Full MS/dd-MS2 mode. Xcalibur 4.0 software was used to control instruments and to collect data, and TraceFinder 3.3 was used for screening and identification. Results: The method's detection limits for 34 drugs and their metabolites in blood, urine and hair samples were 3.30-10700 ng/L, 4.43-5440 ng/L, 0.0350-4.21 µg/kg, respectively. The intra-day and inter-day precisions of the spiked samples at the levels of 5.0, 10, and 20 µg/L were 3.50%-6.00% and 4.18%-9.90%, respectively. A total of 1125 biological samples of urine, blood and hair were collected and screened. The results showed that 96.7% of the drug users were taking a single drug, while 3.3% were mixed drug users. The main types of drug of abuse were methamphetamine (75.8%), heroin (18.5%), ketamine (2.4%) and other drugs (3.3%), and 87.9% of the positive samples were from male users. Compared with the results of high-performance liquid chromatography triple quadrupole mass spectrometry, this method can be used to identify more types of drugs in one run and to conduct retrospective analysis. Conclusion: The method established in the study is simple and sensitive and is well suited for the screening of common drugs and metabolites in biological samples.

[Determination of halogenated carboxylic acids in drinking water by ion chromatography-orbitrap mass spectrometry method].

OBJECTIVE: To establish a method for determination of the common and emerging halogenated carboxylic acids(HCAs) in drinking water by ion chromatography(IC) and quadrupole-orbitrap(Q-Orbitrap) high resolution mass spectrometry(HRMS) combined the traditional quantitative detection with semi-target analysis. METHODS: Effects on the type of chromatographic column, the composition of mobile phase, the flow rate of acetonitrile added post column, the column temperature, and the injection volume were studied in detail for IC-HRMS method, also for HRMS conditions. Drinking water sample was directly injected into IC-HRMS for analysis after filtration. The chromatography separation was performed on an AS21 anion exchange chromatography column(2 mm×250 mm) with the gradient elution using 800 mmol/L methylamine-water as mobile phase, and acetonitrile was added after column. The detection was conducted on HRMS with the electrospray ionization negative mode. And the quantitative analysis of 8 haloacetic acids(HAAs) and semi-target screening of 19 HCAs were achieved by full MS/dd-MS~2 mode. RESULTS: Good linearity(r>0.996) was obtained for each of 8 HAAs for IC-HRMS. The method detection limits(MDLs) and method quantification limits(MQLs) were in the range of 0.50-2.5 µg/L and 1.7-8.3 µg/L, respectively. Intra-and inter-day relative standard deviations(RSDs) were in the range of 1.50%-11.0% and 4.58%-10.9%, respectively. The recoveries were in the range of 61.3%-117%(n=6). The proposed method was applied to analyze 39 drinking water samples, and dichloroacetic acid and trichloroacetic acid were detected and quantified, with concentrations ranging from 1.35 to 48.0 µg/L. Besides, five HCAs(difluoroacetic acid, trifluoroacetic acid, bromochloroacetic acid, monochloropropionic acid and dichloropropionic acid) were preliminary identified with semi-target screening method. CONCLUSION: The developed method was simple, rapid, no sample preparation except filtration and low reagent cosumption, which could meet the need of drinking water monitoring and achieve comprehensive screening of HCAs in drinking water. In addition, full MS/dd-MS~2 data acquisition mode could provide retrospective analysis of existing data by adding the emerging or interesting HCAs into the screening compound database.

Optoplasmonic Hybrid Materials for Trace Detection of Methamphetamine in Biological Fluids through SERS.

Optoplasmonic materials comprising both photonic and plasmonic elements are of particular interest for the development of substrates for surface-enhanced Raman spectroscopy (SERS). In this work, a layer of analyte-carrying dielectric nano/microspheres is placed on top of a monolayer of gold nanoparticles to enhance the intensity of the electric (E-) field localization and to enrich the analyte close to the electromagnetic hot spots. Numerical simulations of the hybrid structure confirm an increased and spatially expanded E-field enhancement at the interface. Due to a decreasing filling fraction with increasing size of the dielectric spheres, simulations predict a saturated SERS enhancement for dielectric microspheres with a diameter larger than 4 µm, which is confirmed by experimental SERS measurements. The dielectric microsphere can be functionalized with surface ligands that facilitate the binding of target molecules in solution. The deposition of the analyte-loaded microspheres on the self-assembled gold nanoparticle ensures a high local concentration of analytes in the electromagnetic "hot" surface. The performance of the optoplasmonic SERS approach for detecting methamphetamine in saliva and urine is tested, and the detection of analytes at nanomolar (nM) concentrations is demonstrated.

Rapid and simple analysis of amphetamine-type illegal drugs using excitation-emission matrix fluorescence coupled with parallel factor analysis.

Nowadays, the abuse of illegal drugs has been an increasingly grim problem in the world. Excitation-emission matrix fluorescence combined with parallel factor analysis was used to make a quantitative analysis of the simulated amphetamine-type illegal drugs. Satisfactory results were achieved for simultaneous determination of methamphetamine (MAM) and 3, 4-methylenedioxymethamphetamine (MDMA) in the presence of adulterants. The average recoveries were (99.8 ± 0.6)% and (101.6 ± 5.7)% for MAM and MDMA, respectively. Figures of merit including root-mean-square error of calibration and prediction, sensitivity and selectivity were investigated to evaluate the performance of the proposed method. The limits of detection were 0.054 and 0.002 1 µg/mL for MAM and MDMA, respectively.