Polymer-spray mass spectrometric detection and quantitation of hydrophilic compounds and some narcotics.

RATIONALE: High-throughput screening of biofluids is essential in monitoring concentration of a variety of drugs to determine their efficacy and toxicity. Organosiloxane polymers prepared by sol-gel chemistry as sample supports, and electrospray ionization emitters in a single material and as an alternative to paper substrates, is described in this study. METHODS: Hydrophobic drugs and hydrophilic streptomycin were analyzed by polymer-spray mass spectrometry with an LTQ-Orbitrap mass spectrometer. Drug samples in urine (1-2 µL) were deposited on an OSX polymer, allowed to dry, then electrosprayed from the polymer tip into the mass spectrometer without sample pretreatment. The OSX polymers, whose polarity and porosity can be controlled, were prepared by sol-gel chemistry where methyl-substituted alkoxysilanes were hydrolyzed in the presence of a pore template and an acid catalyst. RESULTS: Five nanograms each of seven narcotic drugs were detected in <1 min (relative standard deviation (RSD) of response <1% for each drug). Calibration curves of cocaine and streptomycin in urine were used to establish the performance of the polymer. For sample 1 (n = 2), the mean recovery for cocaine was 81% with paper and 90% with polymer. Streptomycin is detected with polymer, not with paper; for samples 1 and 2 (n = 3), mean recovery was 97% and 95%, respectively. CONCLUSIONS: Organosiloxane polymers achieve more sensitive analysis than paper, allowing for more accurate quantitation of both hydrophobic and hydrophilic drug compounds. The ability to tailor the polymer polarity and porosity allows for the synthesis of a wide range of polymers, and thus opens many possibilities for further development and applications.

Direct fluorescence anisotropy assay for cocaine using tetramethylrhodamine-labeled aptamer.

Development of simple, sensitive, and rapid method for cocaine detection is important in medicine and drug abuse monitoring. Taking advantage of fluorescence anisotropy and aptamer, this study reports a direct fluorescence anisotropy (FA) assay for cocaine by employing an aptamer probe with tetramethylrhodamine (TMR) labeled on a specific position. The binding of cocaine and the aptamer causes a structure change of the TMR-labeled aptamer, leading to changes of the interaction between labeled TMR and adjacent G bases in aptamer sequence, so FA of TMR varies with increasing of cocaine. After screening different labeling positions of the aptamer, including thymine (T) bases and terminals of the aptamer, we obtained a favorable aptamer probe with TMR labeled on the 25th base T in the sequence, which exhibited sensitive and significant FA-decreasing responses upon cocaine. Under optimized assay conditions, this TMR-labeled aptamer allowed for direct FA detection of cocaine as low as 5 µM. The maximum FA change reached about 0.086. This FA method also enabled the detection of cocaine spiked in diluted serum and urine samples, showing potential for applications. Graphical Abstract The binding of cocaine to the TMR-labeled aptamer causes conformation change and alteration of the intramolecular interaction between TMR and bases of aptamer, leading to variance of fluorescence anisotropy (FA) of TMR, so direct FA analyis of cocaine is achieved.

Resonance Rayleigh scattering technique as a detection method for the RP-HPLC determination of local anaesthetics in human urine.

A highly selective and sensitive method of reversed phase high-performance liquid chromatography (RP-HPLC) coupled with resonance Rayleigh scattering (RRS) was developed for the determination of procaine, bupivacaine and tetracaine. Separation of three local anaesthetics was achieved at 35 °C on a C18 column. The mobile phase was 30: 70 (v/v) acetonitrile/triethylamine-phosphoric acid buffer (pH 2.9) at flow rate of 0.3 mL/min. The RRS detection was conducted by taking advantage of the strong RRS enhancement of the local anaesthetics with erythrosine reaction in an acidic medium. Under optimum conditions, the limit of detection (S/N = 3) values were in the range of 2.4-11.2 ng/mL. Recoveries from spiked human urine samples were 95.8%-104.5%. The proposed method applied to the determination of local anaesthetics in human urine achieved satisfactory results. In addition, the mechanism of the reaction is fully discussed. Copyright © 2016 John Wiley & Sons, Ltd.

On-line preconcentration strategy for the simultaneous quantification of three local anesthetics in human urine using CZE.

The simultaneous determination of usually employed anesthetics (procaine, lidocaine, and bupivacaine) has been developed and validated using CE with ultraviolet detection at 212 nm. The separation of these three drugs has been achieved in less than 7 min, using a temperature of 25ºC and 25 kV, with a 150 mM citrate buffer (pH 2.5) as BGE. Field-amplified sample injection (FASI) has been used for on-line sample preconcentration. Ultrapure water and ACN 50/50 (v/v) mixture gave the greatest enhancement factor when it was employed as an injection solvent. Injection voltage and time were optimized, being 13 kV and 13 s, the optimum values, respectively. To avoid the possible irreproducibility associated with the electrokinetic injection, an internal standard such as tetracaine, was employed. The instrumental detection limits (LOD S/N = 3) for the compounds ranged between 2.6 and 7.0 µg L(-1) and the quantitation limits (LOQ S/N = 10) between 37.8 and 55.9 µg L(-1) . The detection limits obtained in real human urine samples ranged between 55.2 and 83.6 µg L(-1) and the quantitation limits between 196.0 and 276.0 µg L(-1) . The proposed method has demonstrated its applicability to the analysis of these local anesthetics in urine samples without any pretreatment, allowing the rapid determination of these target analytes.

Investigations into distribution of lidocaine in human autopsy material.

With screening methods in the legal medicine drugs were often detected in autopsy material. In this study the antiarrhythmic and the local anesthetic drug lidocaine could be proved in fifty-one cases and determined in different autopsy materials. For the first time the comparison of so many distribution patterns of lidocaine in human compartments was possible. A liquid-liquid extraction procedure, a standard addition method and LC/MS/MS were used for analytics. The measured concentrations in blood were in the therapeutic range or lower. The time between lidocaine application and death was given in twenty-nine cases. These data were very helpful to estimate and interpret the distribution process of lidocaine between application and death. This time exerted a crucial influence on the distribution of lidocaine in the compartments. Most of the intravenous applicated lidocaine was found in heart blood after a very short time of distribution. Afterwards the highest concentrations were measured in brain. Later the highest concentration was found in the kidney samples or in urine. If the time between lidocaine application and death is known, the results of this study can be used to deepen the knowledge of its pharmacokinetics. If this time is unknown, the circumstances and the causes of death can be better explained.

Molecularly imprinted polymer in microextraction by packed sorbent for the simultaneous determination of local anesthetics: lidocaine, ropivacaine, mepivacaine and bupivacaine in plasma and urine samples.

This study presents the use of molecularly imprinted polymer (MIP) as packing material for microextraction by packed syringe (MEPS) to achieve higher extraction selectivity. Pentycaine was used as template for MIP. Development and validation of the determination of lidocaine, ropivacaine, mepivacaine and bupivacaine in human plasma and urine samples utilizing MIP-MEPS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were carried out. The MEPS MIP-cartridge could be used for 100 extractions before it was discarded. The extraction recovery ranged from 60 to 80%. The correlation coefficients values were >0.999 for all assays using lidocaine, ropivacaine, mepivacaine and bupivacaine in the calibration range 5-2000 nmol/L. The accuracy of the studied compounds, given as a percentage variation from the nominal concentration values, ranged from -4.9 to 8.4% using plasma and urine samples. The between-batch precision, given as the relative standard deviation, at three different concentrations (quality control samples) was ranged from -4.7 to 14.0% and from 1.8 to 12.7% in plasma and urine, respectively. The lower limit of quantification and limit of detection of the studied substances were 5.0 and 1.0 nm, respectively.

Determination of tetracaine hydrochloride by fluorescence quenching method with some aromatic amino acids as probes.

A novel fluorescence quenching method for the determination of tetracaine hydrochloride (TA·HCl) concentration with some aromatic amino acids as fluorescence probe has been developed. In pH 6.3 acidic medium, tryptophane (Trp), tyrosine (Tyr) or phenylalanine (Phe) can react with tetracaine hydrochloride to form an ion-association complex by electrostatic attraction, aromatic stacking interaction and Van der Waals' force, which lead to fluorescence quenching of above amino acids. The maximum fluorescence excitation and emission wavelengths of them are located at 278, 274, 258 nm and 354, 306, 285 nm, respectively. The relative fluorescence intensity (F (0)/F) is proportional to the TA·HCl concentration in certain range. The linear ranges and detection limits are 1.2-5.0 µg/mL and 0.37 µg/mL for Tyr-TA·HCl system, 1.3-6.0 µg/mL and 0.38 µg/mL for Trp-TA·HCl system, and 1.4-6.0 µg/mL and 0.41 µg/mL for Phe-TA·HCl system. The optimum reaction conditions, influencing factors and the effect of coexisting substances are investigated. And the results show the method has a good selectivity. Judging from the effect of temperature, the Stern-Volmer plots and fluorescence lifetime determination, the quenching of fluorescence of amino acids by TA·HCl is a static quenching process.

Utility of cocaine drug screens to predict safe delivery of general anesthesia for elective surgical patients.

Cocaine has been associated with acute hemodynamic changes, causing anesthesia providers to be concerned about adverse hemodynamic events during general anesthesia. We sought to determine if there were differences in the prevalence of adverse hemodynamic events, and if hemodynamic instability could be predicted in cocaine-positive patients undergoing general anesthesia for elective surgery. A retrospective cohort study was conducted in 300 (150 cocaine-positive, 150 cocaine-negative) consecutive adults with similar general anesthesia plans who were hemodynamically normal at baseline. Subjects were excluded if they were not alert at baseline, or if they required more than 1 surgical procedure. Slightly more than 50% of subjects were female, but cocaine-positive subjects were significantly more likely to be male (chi2 = 5.9; P = .02). Baseline systolic pressure (P = .001; mean difference, 6.5 mm Hg; 95% confidence interval [CI], 2.7-70.2), mean arterial pressure (P = .04; mean difference, 2.9 mm Hg; 95% CI, 1.0-5.7), and heart rate (P = .02; mean difference, 3.3/min; 95% CI, 0.46-6.2) were significantly higher, but not clinically important in the cocaine-positive cohort. Our study demonstrates that use of drug screen results alone is insufficient to predict the safe administration of general anesthesia in patients undergoing elective surgeries.

Analysis of drugs of abuse in biofluids by low temperature plasma (LTP) ionization mass spectrometry.

Low temperature plasma (LTP) ionization is an ambient plasma ionization method that permits the direct mass analysis of samples in their native atmospheric environment with little or no sample preparation. In this work, the low temperature plasma probe is used in the direct and rapid mass spectrometric analysis of aqueous phase samples including biofluids (saliva, urine, and hair extract). A detailed trace qualitative examination of 14 drugs of abuse has been performed. The relative standard deviation on average was approximately 16% for the LTP analysis of the drugs of abuse standards. Eleven of the fourteen drugs of abuse were detected in the low ng mL(-1) (3 pg absolute detection) to the mid microg mL(-1) (approximately 30 ng absolute detection) concentration range. One drug, cannabidiol, could not be detected until supplemental heating of the substrate was incorporated into the experimental protocol. The addition of supplemental heating improved the detection limits by at least an order of magnitude to approximately 0.5 ng mL(-1) to 0.5 microg mL(-1) (1.5 pg-1.5 ng absolute) for twelve of the fourteen drugs of abuse, so extending the linear dynamic range which for most analytes was four orders of magnitude. Quantitative capabilities were evaluated using the particular example of benzoylecgonine in urine by employing a deuterated internal standard. Matrix effects observed during the analysis of the drugs in complex biological fluids are also discussed. In addition, low temperature plasma ionization was applied to the examination of real (not spiked) biological samples and these results were confirmed using standard LC/MS methodology. The main advantages observed for this ambient desorption/ionization technique include the capabilities for direct analysis of liquid surfaces for in situ detection and the remarkable sensitivity in the examination of the drugs of abuse investigated here. The disadvantages of the method include the modest quantitative accuracy making LTP most useful as a rapid but semi-quantitative screening method.

[Decomposition kinetics of bupivacaine in biological specimens].

OBJECTIVE: To study on the decomposition kinetics of bupivacaine in brain, blood and urine, which were collected from dogs executed by bupivacaine and stored in different conditions. METHODS: Dogs were given arachnoid cavity anesthesia with bupivacaine. Then the brain, blood and urine were collected and divided equally to three groups stored in 20, 4 and -20 degrees C respectively. The concentrations of bupivacaine at different days were determined by the GC. The equation and half-time period of decomposition kinetics were imitated and calculated with WinNolin program. RESULTS: The decomposition kinetics of bupivacaine in the dogs' brain, blood and urine were fit to the first order kinetics. The common equation was lgC = lgCo-kt/2.303 and k was the decomposition constant of first order reaction. CONCLUSION: Bupivacaine in the brain, blood and urine specimens were found to be decomposed at various environments for storage. The higher temperature for storage, the faster of decomposition reaction.

Structural elucidation of amino amide-type local anesthetic drugs and their main metabolites in urine by LC-MS after derivatization and its application for differentiation between positional isomers of prilocaine.

The demand for clinical toxicology analytical methods for identifying drugs of abuse and medicinal drugs is steadily increasing. Structural elucidation of amino amide-type local anesthetic drugs and their main metabolites by GC-EI-MS and LC-ESI-MS/MS is of great analytical challenge. These compounds exhibit only/mostly fragments/product ions representing the amine-containing residue, while the aromatic amide moiety remains unidentified. This task becomes even more complicated when discrimination between positional isomers of such compounds is required. Here, we report the development of a derivatization procedure for the differentiation and structural elucidation of a mixture of local anesthetic drugs and their metabolites that possess tertiary and secondary amines in water and urine. A method based on two sequential "in-vial" instantaneous derivatization processes at ambient temperature followed by LC-ESI-MS/MS analysis was developed. 2,2,2-Trichloro-1,1-dimethylethyl chloroformate (TCDMECF) was utilized to selectively convert the secondary amines into their carbamate derivatives, followed by hydrogen peroxide addition to produce the corresponding tertiary amine oxides. The resulting derivatives exhibited rich fragmentation patterns, enabling improved structural elucidation of the original compounds. The developed method was successfully applied to the differentiation and structural elucidation of prilocaine and its four positional isomers, which all possess similar GC and LC retention times and four of them exhibit almost identical EI-MS and ESI-MS/MS spectra, enabling their structural elucidation in a single LC-ESI-MS/MS analysis. The developed technique is fast and simple and enables discrimination between isomers based on different diagnostic ions/fragmentation patterns.

Acute toxicity evaluation of proliferol: a dose-escalating, placebo-controlled study in swine.

Prolotherapy is one of the many treatments available for chronic musculoskeletal disorders. A commonly used drug contains dextrose 12.5%, glycerin 12.5%, phenol 1.0%, and lidocaine hydrochloride 0.25% in aqueous solution (recently termed Proliferol). For chronic low back pain, this is injected into lumbosacral ligaments to stimulate connective tissue repair. Despite generally positive clinical results, the toxicity of this drug is not well characterized and was assessed in 48 (24 male, 24 female) Yucatan miniature swine randomly assigned to low (1x), medium (5x), or high (10x) dose or saline placebo. Outcomes included clinical observations, clinical chemistry, hematology, coagulation, urinalysis, toxicokinetics, and full gross and microscopic histopathology after 24 hours or 14 days. Findings attributable to Proliferol after 24 hours included dose-response elevations in alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase, which returned to normal after 14 days. There were no remarkable findings in hematology, coagulation, or urinalysis. Urine concentrations of lidocaine and phenol both peaked after 8 hours. Histopathology findings after 24 hours included hemorrhage, inflammation, necrosis, and vascular changes in the ligaments and adjacent soft tissues at the sites of injection. After 14 days, there was evidence of repair under way, with fibrosis and skeletal muscle regeneration at the injection sites.

[Detection of certain local anesthetics in biological fluids by chemo-toxicological analysis].

Analytical procedures for the detection of certain local anesthetics (including lidocaine, trimecaine, articaine, and anilocaine) in blood and urine are described with special reference to their application in chemotoxicological studies. The description is focused on the methods for isolation of the assay preparations from biological fluids and their identification with the help of up-to-date chromatographic techniques, such as thin layer chromatography, high performance liquid chromatography, and gas-liquid chromatography.

Stable plasma concentrations of unbound ropivacaine during postoperative epidural infusion for 24-72 hours in children.

BACKGROUND AND OBJECTIVES: The aim of this open, non-controlled, multi-centre study was to evaluate the pharmacokinetics and safety of a 24-72 h continuous epidural ropivacaine infusion in children aged 1-9 yr. METHODS: After induction of general anaesthesia, 29 ASA I-II children, scheduled for major surgery in dermatomes below T10 had lumbar epidural catheters placed. A bolus of ropivacaine, 2 mg kg(-1), was given over 4 min, followed immediately by an infusion of 2 mg mL(-1) ropivacaine 0.4 mg kg(-1) h(-1) for the next 24-72 h. RESULTS: Plasma concentrations of total ropivacaine (mean 0.83 and 1.06 mg L(-1) at 16-31 and 59-72 h, respectively) and alpha1-acid-glucoprotein (mean 13 and 25 micromol L(-1) at baseline and 59-72 h) increased over the course of the infusion. Plasma concentrations of unbound ropivacaine were stable throughout the epidural infusion (mean 0.021 range 0.011-0.068 and mean 0.016 range 0.009-0.023 mg L(-1) at 16-31 and 59-72 h, respectively) and were well below threshold levels associated with central nervous system toxicity in adults (0.35 mg L(-1)). Apparent unbound clearance (mean 346, range 86-555 mL min(-1) kg(-1)) showed no age-dependency. No signs of systemic toxicity or cardiovascular effects were observed. All patients received additional analgesics with morphine. CONCLUSION: Following a 24-72 h epidural infusion of ropivacaine 0.4 mg kg(-1) h(-1) in 1-9-yr-old children, the plasma concentrations of unbound ropivacaine were stable over time with no age-dependency.

An aptamer folding-based sensory platform decorated with nanoparticles for simple cocaine testing.

The consumption of illicit drugs such as cannabis, cocaine, and amphetamines is still a major health and social problem, creating an abuse in adults especially. Novel techniques which estimate the drug of abuse are needed for the detection of newly revealed psychoactive drugs. Herein, we have constructed a combinatorial platform by using quantum dots (QDs) and gold nanoparticles (AuNPs) as well as a functional aptamer which selectively recognizes cocaine and its metabolite benzoylecgonine (BE). We have called it an aptamer folding-based sensory device (AFSD). For the fabrication of AFSD, QDs were initially immobilized onto the poly-L-lysine coated µ-well surfaces. Then, the AuNP-aptamer conjugates were bound to the QDs. The addition of cocaine or BE caused a change in the aptamer structure which induced the close interaction of AuNPs with the QDs. Hence, quenching of the fluorescence of QDs was observed depending on the analyte amount. The linearity of cocaine and BE was 1.0-10 nM and 1.0-25 µM, respectively. Moreover, the limits of detection for cocaine and BE were calculated as 0.138 nM and 1.66 µM. The selectivity was tested by using different interfering substances (methamphetamine, bovine serum albumin, codeine, and 3-acetamidophenol). To investigate the use of AFSD in artificial urine matrix, cocaine/BE spiked samples were applied. Also, confirmatory analyses by using high performance liquid chromatography were performed. It is shown that AFSD has a good potential for testing the cocaine abuse and can be easily adapted for detection of various addictive drugs by changing the aptamer according to desired analytes. Copyright © 2016 John Wiley & Sons, Ltd.

Liquid-phase microextraction combined with high-performance liquid chromatography for the determination of local anaesthetics in human urine.

A simple liquid-phase microextraction (LPME) device combined with high-performance liquid chromatography (HPLC) is presented for the simultaneous analysis of local anaesthetics, lidocaine, bupivacaine, and tetracaine, from human urine sample. An organic solvent showed good compatibility with the mobile phase of the HPLC, o-dibutyl phthalate, was selected. Local anaesthetics are extracted from 6 ml of the feed aqueous solution and human urine sample into a water-immiscible organic solvent suspended at the needle tip of the microsyringe, then the organic solvent was directly introduced to a reversed-phase HPLC system. The kind of the organic extraction solvent, the stirring rate, the pH value of the aqueous feed solution, and the extraction time have been discussed. Under the optimized extraction conditions, high enrichment factors (more than 86.0-fold) and significant sample clean-up for all of studied local anaesthetics were achieved within 30 min. The detection limits (lower than 0.05 microg/ml) were comparable with previously reported gas chromatography methods. This method was applied to specimen of patient who was treated with extradural anaesthesia of lidocaine, bupivacaine, and tetracaine, and revealed that simultaneous determination of above three local anaesthetics in human urine was possible.

A high-performance thin-layer chromatographic technique to screen cocaine in urine samples.

Qualitative identification of cocaine and its metabolites in urine samples is generally carried out by an immunoassay technique followed by a gas chromatographic/mass spectrometric confirmation of presumptive positives. Nevertheless, other chromatographic techniques such as thin-layer chromatography or gas chromatography could also be used to screen several types of drugs of abuse especially for forensic and legal purposes. In the present work, the capability of high performance thin-layer chromatography (HPTLC) to detect cocaine in urine samples and discriminate it from interfering substances (local anaesthetic, caffeine and nicotine) was studied. Twenty urine samples of drug addicts were submitted to the HPTLC method. Unaltered cocaine present in the urine samples and cocaine obtained after methylation of benzoylecgonine (main cocaine metabolite) with diazomethane were detected in all tested samples. In conclusion, the proposed HPTLC method showed to be useful to detect cocaine in biological matrices.

Ciprofloxacin bioavailability is enhanced by oral co-administration with phenazopyridine: a pharmacokinetic study in a Mexican population.

BACKGROUND: and objective: In Mexico, urinary tract infections (UTIs) constitute the second most frequent type of infections treated at primary-care clinics. Ciprofloxacin has played a major role in the treatment of UTIs because it has a broad spectrum of antibacterial activity. In addition to antimicrobial agents, phenazopyridine has been used to alleviate symptoms that occur during episodes of UTI. Thus, the present study was designed to compare the pharmacokinetic behaviour of ciprofloxacin administered alone versus ciprofloxacin combined with phenazopyridine. PATIENTS AND METHODS: Twenty-four healthy male Mexican volunteers participated in this project. The study was carried out with a single oral dose of ciprofloxacin 500mg. The double-blind, crossover, randomised, balanced trial design comprised two treatments, two periods and two sequences. After administration of the study medication, serial blood samples were collected for a period of 12 hours. The harvested plasma was analysed for ciprofloxacin by high-performance liquid chromatography. The area under the concentration-time curve to last measurable concentration (AUC(t)), area under the concentration-time curve extrapolated to infinity (AUC(infinity)), peak plasma concentration (C(max)), time to reach C(max) (t(max)), mean residence time (MRT), elimination constant (k(e)) and elimination half-life (t(1/2)) were determined from plasma concentrations of both treatments and considered as primary variables for statistical analysis. RESULTS: While there were no differences between the two treatments in terms of C(max) and k(e), AUC(t )and AUC(infinity) were 35% and 29% higher, respectively, in the combined treatment arm. Moreover, a significant delay in t(max )(from 1 to 1.5 hours) and a statistical increase of 29% in MRT were also observed with phenazopyridine co-administration. CONCLUSION: Oral co-administration of phenazopyridine increases ciprofloxacin bioavailability with regard to the amount absorbed (AUC) and permanence in the body (MRT), which could be useful during treatment.

Application of solid-phase microextraction to antidoping analysis: determination of stimulants, narcotics, and other classes of substances excreted free in urine.

This paper describes the application of solid-phase microextraction (SPME) with subsequent injection in a gas chromatograph-mass spectrometer (GC-MS) (electron impact, full scan) for the screening analysis of stimulants and narcotics in urine. Several different kinds of fibers were preliminarily tested and comparatively evaluated considering the influence on the overall analytical performance of the method; other experimental parameters; and, primarily among them, the volume of urine, the pH value, and the time of adsorbtion. The optimal experimental conditions have been recorded using 0.5 mL of urine with the pH value adjusted to 10 with carbonate buffer, and in which is immersed a polydimethylsiloxane/divinylbenzene fiber, with a sampling time of 30 min; the fiber is then directly desorbed in the injection port of the GC-MS equipment. All the analytes show a good linearity (R2 > 0.99 for most substances) and a good reproducibility at the concentration corresponding to the minimum performance requirement limit or at the cut-off value fixed by the World AntiDoping Agency (CV% < 11). The limit of detection of the method is 50 ng/mL for the majority of the substances investigated. Imidazole-based drugs (e.g., naphazoline) and local anesthetics can also be included in this screening method. Whenever necessary, confirmation analyses may also be performed by following the same pre-chromatographic procedure. Integrating the SPME process and the GC-MS analysis with a dedicated autosampler that combines the microextraction and injection capacities maximizes the overall analytical capacity of a single GC-MS system and reduces the human labor necessary for and the environmental impact of screening for stimulants and narcotics excreted free in urine.

A competitive strategy based on cucurbit[7]uril supramolecular interaction for simple and sensitive detection of dibucaine.

In this work, the competitive interaction between dibucaine and three fluorescent probes (i.e., berberine, palmatine, and coptisine) for occupancy of the cucurbit[7]uril (CB[7]) cavity was studied by fluorescence spectra, UV-visible absorption spectra, (1)H NMR spectra, and theoretical calculations in acidic aqueous solution. Based on the fluorescence enhancement of berberine, palmatine, and coptisine upon binding with CB[7], respectively, a series of fluorescence detection methods for dibucaine were proposed. At the optimized conditions, the fluorescence intensity of berberine-CB[7], palmatine-CB[7], and coptisine-CB[7] complexes showed negative correlation to the concentration of dibucaine, which led to a series of simple and sensitive fluorescence methods for the determination of dibucaine for the first time. Linear ranges obtained in the detection of the dibucaine were 0.018-3.34 µmol L(-1), 0.032-4.47 µmol L(-1), and 0.079-4.42 µmol L(-1) with detection limits of 6.0 nmol L(-1), 12.0 nmol L(-1), and 25.0 nmol L(-1), respectively. Moreover, the proposed method was successfully applied for the determination of the drug in biological fluids. The competitive mode based on CB[7] superstructure provided a promising assay strategy for fluorescence detection in various potential applications.