Design of resonance Rayleigh scattering and spectrofluorimetric methods for the determination of the antihistaminic drug, hydroxyzine, based on its interaction with 2,4,5,7-tetraiodofluorescein: Evaluation of analytical eco-scale and greenness/whiteness algorithms.

In this work, two validated approaches were used for estimating hydroxyzine HCl for the first time using resonance Rayleigh scattering (RRS) and spectrofluorimetric techniques. The suggested approaches relied on forming an association complex between hydroxyzine HCl and 2,4,5,7-tetraiodofluorescein (erythrosin B) reagent in an acidic media. The quenching in the fluorescence intensity of 2,4,5,7-tetraiodofluorescein by hydroxyzine at 551.5 nm (excitation = 527.5 nm) was used for determining the studied drug by the spectrofluorimetric technique. The RRS approach is based on amplifying the RRS spectrum at 348 nm upon the interaction of hydroxyzine HCl with 2,4,5,7-tetraiodofluorescein. The spectrofluorimetric methodology and the RRS methodology produced linear results within ranges of 0.15-1.5 µg ml-1 and 0.1-1.2 µg ml-1, respectively. LOD values for these methods were determined to be 0.047 µg ml-1 and 0.033 µg ml-1, respectively. The content of hydroxyzine HCl in its pharmaceutical tablet was estimated using the developed procedures with acceptable recoveries. Additionally, the application of four greenness and whiteness algorithms shows that they are superior to the previously reported method in terms of sustainability, economics, analytical performance, and practicality.

Trace analysis of 20 antihistamines in milk by ultrahigh performance liquid chromatography coupled with high field quadrupole orbitrap high resolution mass spectrometry followed dispersive micro solid phase extraction.

Ultrahigh-performance liquid chromatography coupled with high-field quadrupole Orbitrap high resolution mass spectrometry was used for the separation and determination of 20 antihistamines, and a dispersive micro solid-phase extraction procedure using high-performance absorbing material was developed as a sample preparation strategy for extracting 20 antihistamines from milk. Instrument conditions and key parameters influencing extraction efficiency were investigated to obtain an optimized method. The limit of detection for 20 antihistamines in milk using this method is 0.05 µg/L to 1.0 µg/L. Recoveries are between 80.7 % and 108.3 %, and the relative standard deviation is less than 15 %. It is suitable for confirmatory monitoring and quantitative analysis of 20 antihistamines in milk. The results show that antihistamines in milk may be noteworthy issues for human health and environmental pollution.

Microliquid/Liquid Interfacial Sensors: Biomimetic Investigation of Transmembrane Mechanisms and Real-Time Determinations of Clemastine, Cyproheptadine, Epinastine, Cetirizine, and Desloratadine.

Antihistamines relieve allergic symptoms by inhibiting the action of histamine. Further understanding of antihistamine transmembrane mechanisms and optimizing the selectivity and real-time monitoring capabilities of drug sensors is necessary. In this study, a micrometer liquid/liquid (L/L) interfacial sensor has served as a biomimetic membrane to investigate the mechanism of interfacial transfer of five antihistamines, i.e., clemastine (CLE), cyproheptadine (CYP), epinastine (EPI), desloratadine (DSL), and cetirizine (CET), and realize the real-time determinations. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques have been used to uncover the electrochemical transfer behavior of the five antihistamines at the L/L interface. Additionally, finite element simulations (FEMs) have been employed to reveal the thermodynamics and kinetics of the process. Visualization of antihistamine partitioning in two phases at different pH values can be realized by ion partition diagrams (IPDs). The IPDs also reveal the transfer mechanism at the L/L interface and provide effective lipophilicity at different pH values. Real-time determinations of these antihistamines have been achieved through potentiostatic chronoamperometry (I-t), exhibiting good selectivity with the addition of nine common organic or inorganic compounds in living organisms and revealing the potential for in vivo pharmacokinetics. Besides providing a satisfactory surrogate for studying the transmembrane mechanism of antihistamines, this work also sheds light on micro- and nano L/L interfacial sensors for in vivo analysis of pharmacokinetics at a single-cell or single-organelle level.

Pharmaceutical Residues in Edible Oysters along the Coasts of the East and South China Seas and Associated Health Risks to Humans and Wildlife.

The investigation of pharmaceuticals as emerging contaminants in marine biota has been insufficient. In this study, we examined the presence of 51 pharmaceuticals in edible oysters along the coasts of the East and South China Seas. Only nine pharmaceuticals were detected. The mean concentrations of all measured pharmaceuticals in oysters per site ranged from 0.804 to 15.1 ng g-1 of dry weight, with antihistamines being the most common. Brompheniramine and promethazine were identified in biota samples for the first time. Although no significant health risks to humans were identified through consumption of oysters, 100-1000 times higher health risks were observed for wildlife like water birds, seasnails, and starfishes. Specifically, sea snails that primarily feed on oysters were found to be at risk of exposure to ciprofloxacin, brompheniramine, and promethazine. These high risks could be attributed to the monotonous diet habits and relatively limited food sources of these organisms. Furthermore, taking chirality into consideration, chlorpheniramine in the oysters was enriched by the S-enantiomer, with a relative potency 1.1-1.3 times higher when chlorpheniramine was considered as a racemate. Overall, this study highlights the prevalence of antihistamines in seafood and underscores the importance of studying enantioselectivities of pharmaceuticals in health risk assessments.

Cationic amphiphilic antihistamines inhibit STAT3 via Ca2+-dependent lysosomal H+ efflux.

Commonly used antihistamines and other cationic amphiphilic drugs (CADs) are emerging as putative cancer drugs. Their unique chemical structure enables CADs to accumulate rapidly inside lysosomes, where they increase lysosomal pH, alter lysosomal lipid metabolism, and eventually cause lysosomal membrane permeabilization. Here, we show that CAD-induced rapid elevation in lysosomal pH is caused by a lysosomal H+ efflux that requires P2RX4-mediated lysosomal Ca2+ release and precedes the lysosomal membrane permeabilization. The subsequent cytosolic acidification triggers the dephosphorylation, lysosomal translocation, and inactivation of the oncogenic signal transducer and activator of transcription 3 (STAT3) transcription factor. Moreover, CAD-induced lysosomal H+ efflux sensitizes cancer cells to apoptosis induced by STAT3 inhibition and acts synergistically with STAT3 inhibition in restricting the tumor growth of A549 non-small cell lung carcinoma xenografts. These findings identify lysosomal H+ efflux and STAT3 inhibition as anticancer mechanisms of CADs and reinforce the repurposing of safe and inexpensive CADs as cancer drugs with a drug combination strategy.

Ultrasonication-aided synthesis of nanoplates-like iron molybdate: Fabricated over glassy carbon electrode as an modified electrode for the selective determination of first generation antihistamine drug promethazine hydrochloride.

The innovation of novel and proficient nanostructured materials for the precise level determination of pharmaceuticals in biological fluids is quite crucial to the researchers. With this in mind, we synthesized iron molybdate nanoplates (Fe2(MoO4)3; FeMo NPs) via simple ultrasonic-assisted technique (70 kHz with a power of 100 W). The FeMo NPs were used as the efficient electrocatalyst for electrochemical oxidation of first-generation antihistamine drug- Promethazine hydrochloride (PMH). The as-synthesized FeMo NPs were characterized and confirmed by various characterization techniques such as XRD, Raman, FT-IR, FE-SEM, EDX and Elemental mapping analysis and electron impedance spectroscopy (EIS). In addition, the electrochemical characteristic features of FeMo NPs were scrutinized by electrochemical techniques like cyclic voltammetry (CV) and differential pulse voltammetry technique (DPV). Interestingly, the developed FeMo NPs modified glassy carbon electrode (FeMo NPs/GCE) discloses higher peak current with lesser anodic potential on comparing to bare GCE including wider linear range (0.01-68.65 µM), lower detection limit (0.01 µM) and greater sensitivity (0.97 µAµM-1cm-2). Moreover, the as-synthesized FeMo NPs applied for selectivity, reproducibility, repeatability and storage ability to investigate the practical viability. In the presence of interfering species like cationic, anionic and biological samples, the oxidation peak current response doesn't cause any variation results disclose good selectivity towards the detection of PMH. Additionally, the practical feasibility of the FeMo NPs/GCE was tested by real samples like, commercial tablet (Phenergan 25 mg Tablets) and lake water samples which give satisfactory recovery results. All the above consequences made clear that the proposed sensor FeMo NPs/GCE exhibits excellent electrochemical behavior for electrochemical determination towards oxidation of antihistamine drug PMH.

High performance liquid chromatography associated with resonance Rayleigh scattering for synchronous determination of three antihistamines and mechanism study.

A highly sensitive and selective method of high performance liquid chromatography (HPLC) combined with resonance Rayleigh scattering (RRS) spectra was developed for the detection of three antihistamine drugs, including pyrilamine (PY), carbinoxamine (CAR) and tripelennamine (TRI). The three antihistamines were separated by a C18 column. The mobile phase contained 25% acetonitrile (ACN) and 75% phosphate buffered solution (pH 3.2) with the flow rate of 0.4 ml min-1 . In medium of Britton-Robinson (BR) buffer solution (pH 4.6), the PY, CAR and TRI separated by HPLC and then reacted with Erythrosine B (EryB), forming 1:1 ion-association complexes, which led to significant signal enhancement of RRS spectra. The RRS spectra was detected at the wavelength λex =λem = 370 nm. The calibration curves of PY, CAR and TRI were linear in the range from 0.02 to 25 µg ml-1 , and the detection limit [signal-to-noise ratio (S/N) = 3] were 3.38, 4.48 and 5.50 ng ml-1 , respectively. In addition, under the optimum experiment condition, the reaction mechanism and the reasons for RRS enhancement were investigated in this work. The developed method was applied to the simultaneous detection of three antihistamines in water samples with satisfying results.

Population histamine burden assessed using wastewater-based epidemiology: The association of 1,4­methylimidazole acetic acid and fexofenadine.

Systematic sampling and analysis of wastewater has become an important tool for monitoring consumption of drugs and other substances, and has been proposed as a method to evaluate aspects of population health using endogenous biomarkers. 1,4­methylimidazoleacetic acid (MIAA) is an endogenous biomarker and metabolite of histamine turnover. Its urinary excretion is elevated in conditions such as mastocytosis, hay fever, hives, food allergies and anaphylaxis. The aim of this study was to develop and apply methods for MIAA in wastewater and compare its occurrence with antihistamine use in wastewater. Consecutive daily samples were collected from seven catchments serving populations from 3000 to 2 million and covering rural and urban communities during the 2016 Census in Australia. MIAA and the antihistamines (ranitidine, fexofenadine, cetirizine) were quantified consistently. Per capita excretion of MIAA (mg/d/capita) estimated from the WW concentrations were consistent with findings from previous clinical studies. We found significant positive correlations between loads of MIAA and fexofenadine (R2 = 0.68, p < 0.0001) and cetirizine (R2 = 0.25, p = 0.03) across the various catchments. Sewer reactor experiments on the degradation of MIAA and the antihistamines found that fexofenadine is stable for at least 24 h while MIAA, ranitidine and cetirizine are subject to degradation, and this should be considered in interpretations. To the best of our knowledge, this study is the first wastewater study to introduce and monitor an endogenous metabolite of histamine, and the first study to monitor and relate proxies of disease and treatment of disease.

A fully validated method for the simultaneous determination of 11 antihistamines in breast milk by gas chromatography-mass spectrometry.

Antihistamines are excreted into breast milk in small amounts; however, there are no adequate published studies or data concerning their effects on newborns and safety during breastfeeding. Thus, the development of sensitive and specific methodologies for the determination of antihistamines in breast milk is critical. A simple and sensitive GC-MS method for the simultaneous determination of 11 antihistamines (diphenhydramine, orphenadrine, chlorpheniramine, dimethindene, meclozine, hydroxyzine, loratadine, desloratadine, cetirizine, rupatadine and ebastine) in breast milk was developed and validated. The antihistamines were solid-phase extracted and derivatized with acetic anhydride and n-propanol. Diazepam-d5 , hydroxyzine-d4 and cetirizine-d8 were used as internal standards. Absolute recovery values for all analytes ranged from 70.5 to 120.0%, while the limits of detection and quantification for all analytes were 1.50 and 5.00 ng/mL, respectively. All calibration curves were linear (R2 ≥ 0.990) within the range 5.00-1000.0 ng/mL. Accuracy (Er ) ranged between -7.6 and 7.0%, while precision (RSD) was <12% for all antihistamines. The developed method is suitable for the investigation of antihistamine-related clinical cases, as well as for pharmacokinetic and breastfeeding safety studies.

Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period.

Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology. A literature review on concentrations in the published DFC-related hair cases and on concentrations in hair of these substances after single and multiple doses is included. These cases demonstrate the value of segmental hair analysis in DFCs and facilitate future interpretations of results.

Collision-induced dissociation pathways of H1-antihistamines by electrospray ionization quadrupole time-of-flight mass spectrometry.

Over the past decades, mass spectrometry technologies have been developed to obtain mass accuracies of one ppm or less. Of the newly developed technologies, quadrupole time-of-flight mass spectrometry (Q-TOF-MS) has emerged as being well suited to routine and high-throughput analyses of pharmaceuticals. Dietary supplements and functional foods have frequently been found to be contaminated with pharmaceuticals. In our continuous efforts to develop methodologies to protect public health against adulterated dietary supplements, we have constructed a mass spectral database for 21 H1-antihistamines encountered as adulterants by using liquid chromatography-electrospray ionization (LC-ESI)/Q-TOF-MS, and have proposed their possible collision-induced dissociation pathways. This database will be very useful for the rapid and accurate detection of H1-antihistamines (known) and their analogues (unknown) illegally added to dietary supplements as well as in other sample matrices.

New model for prediction binary mixture of antihistamine decongestant using artificial neural networks and least squares support vector machine by spectrophotometry method.

In the present study, artificial neural networks (ANNs) and least squares support vector machines (LS-SVM) as intelligent methods based on absorption spectra in the range of 230-300nm have been used for determination of antihistamine decongestant contents. In the first step, one type of network (feed-forward back-propagation) from the artificial neural network with two different training algorithms, Levenberg-Marquardt (LM) and gradient descent with momentum and adaptive learning rate back-propagation (GDX) algorithm, were employed and their performance was evaluated. The performance of the LM algorithm was better than the GDX algorithm. In the second one, the radial basis network was utilized and results compared with the previous network. In the last one, the other intelligent method named least squares support vector machine was proposed to construct the antihistamine decongestant prediction model and the results were compared with two of the aforementioned networks. The values of the statistical parameters mean square error (MSE), Regression coefficient (R2), correlation coefficient (r) and also mean recovery (%), relative standard deviation (RSD) used for selecting the best model between these methods. Moreover, the proposed methods were compared to the high- performance liquid chromatography (HPLC) as a reference method. One way analysis of variance (ANOVA) test at the 95% confidence level applied to the comparison results of suggested and reference methods that there were no significant differences between them.

Global scanning of antihistamines in the environment: Analysis of occurrence and hazards in aquatic systems.

Concentration of the global population is increasingly occurring in megacities and other developing regions, where access to medicines is increasing more rapidly than waste management systems are implemented. Because freshwater and coastal systems are influenced by wastewater effluent discharges of differential quality, exposures in aquatic systems must be considered. Here, we performed a global scanning assessment of antihistamines (AHs), a common class of medicines, in surface waters and effluents. Antihistamines were identified, literature occurrence and ecotoxicology data on AHs collated, therapeutic hazard values (THVs) calculated, and environmental exposure distributions (EEDs) of AHs compared to ecotoxicity thresholds and drug specific THVs to estimate hazards in surface waters and effluents. Literature searches of 62 different AHs in environmental matrices identified 111 unique occurrence publications of 24 specific AHs, largely from Asia-Pacific, Europe, and North America. However, the majority of surface water (63%) and effluent (85%) observations were from Europe and North America, which highlights relatively limited information from many regions, including developing countries and rapidly urbanizing areas in Africa, Latin America and Asia. Less than 10% of all observations were for estuarine or marine systems, though the majority of human populations reside close to coastal habitats. EED 5th and 95th centiles for all AHs were 2 and 212ng/L in surface water, 5 and 1308ng/L in effluent and 6 and 4287ng/L in influent, respectively. Unfortunately, global hazards and risks of AHs to non-target species remain poorly understood. However, loratadine observations in surface waters exceeded a THV without an uncertainty factor 40% of the time, indicating future research is needed to understand aquatic toxicology, hazards and risks associated with this AH. This unique global scanning study further illustrates the utility of global assessments of pharmaceuticals and other contaminants to identify chemicals requiring toxicology study and regions where environmental monitoring, assessment and management efforts appear limited and necessary.

Validated sensitive spectrofluorimetric method for determination of antihistaminic drug azelastine HCl in pure form and in pharmaceutical dosage forms: application to stability study.

A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of azelastine HCl (AZL) in either its pure state or pharmaceutical dosage form. The proposed method was based on measuring the native fluorescence of the studied drug in 0.2 M H2 SO4 at λem  = 364 nm after excitation at λex  = 275 nm. Different experimental parameters were studied and optimized carefully to obtain the highest fluorescence intensity. The proposed method showed a linear dependence of the fluorescence intensity on drug concentration over a concentration range of 10-250 ng/mL, with a limit of detection of 1.52 ng/mL and limit of quantitation of 4.61 ng/mL. Moreover, the method was successfully applied to pharmaceutical preparations, with percent recovery values (± SD) of 99.96 (± 0.4) and 100.1 (± 0.52) for nasal spray and eye drops, respectively. The results were in good agreement with those obtained by the comparison method, as revealed by Student's t-test and the variance ratio F-test. The method was extended to study the stability of AZL under stress conditions, where the drug was exposed to neutral, acidic, alkaline, oxidative and photolytic degradation according to International Conference on Harmonization (ICH) guidelines. Copyright © 2016 John Wiley & Sons, Ltd.

Screening anti-allergic components of Astragali Radix using LAD2 cell membrane chromatography coupled online with UHPLC-ESI-MS/MS method.

Huangqi (Astragali Radix), a traditional Chinese herb, is widely used in clinical therapy in China. In addition, an anti-allergic effect of constituents in Huangqi has been reported in the scientific literature. In the present study, cell membrane chromatography coupled online with UHPLC-ESI-MS/MS method was developed to screen, analyze and identify the anti-allergic components of Huangqi. The Laboratory of Allergic Disease 2 (LAD2) cell was used to establish cell membrane chromatography, which was combined with UHPLC-ESI-MS/MS. The coupled system was then used to screen anti-allergic components from Huangqi. Effects of active components were verified by histamine release assay. A component retained on the LAD2 cell membrane chromatography was identified as formononetin. Bioactivity of formononetin was investigated by histamine release assay in LAD2 cells, and it was found that formononetin could inhibit histamine release in a dose-dependent manner from 1 to 100 µm. The LAD2 cell membrane chromatography online with UHPLC-ESI-MS/MS method is an effective technique for screening the anti-allergic components of Huangqi.

Development and validation of an ultra-performance liquid chromatography method for simultaneous analysis of 20 antihistaminics in dietary supplements.

The purpose of this study was to develop and validate an ultra-performance liquid chromatography method for simultaneous analysis of 20 antihistamines (illegal additives) in dietary supplements. The limits of detection and quantitation of the method ranged from 1.5 to 2.5 µg/mL and from 20.0 to 50.0 µg/mL, respectively. The determination coefficient was >0.999, precisions were 0.2-5.1% (intra-day) and 0.1-8.8% (inter-day), and accuracies were 84.5-111.2% (intra-day) and 91.9-112.0% (inter-day). The mean recoveries of 20 targeted compounds from dietary supplements ranged from 75.4 to 119.3%. The relative standard deviations were <6.6% and complied with established international guidelines. The relative standard deviation of stability was <0.8%. Fifty-two commercially available dietary supplements were evaluated using this method, and were found to have none of the 20 antihistamines in significant abundance.

Photodegradation of the antihistamine cetirizine in natural waters.

The photodegradation rate of the anti-histamine cetirizine (Zyrtec®) was investigated in various water matrices. The average observed first-order photodegradation rate coefficient (kobs ), obtained by linear regression of the logarithmic-transformed cetirizine concentrations versus irradiation time in simulated sunlight, was 0.024 h(-1) (n = 6; standard deviation ± 0.004) in deionized water corresponding to a half-life of approximately 30 h. There was no statistical difference in the kobs of cetirizine photodegradation in coastal seawater compared with deionized water or deionized water amended with dissolved chromophoric organic matter. The quantum yield of cetirizine photodegradation decreased dramatically with increasing wavelength and decreasing energy of incoming radiation, with the average value ranging from 5.28 × 10(-4) to 6.40 × 10(-3) in the ultraviolet wavelength range (280-366 nm). The activation energy of cetirizine photodegradation was 10.3 kJ mol(-1) with an observed increase in cetirizine photodegradation as temperature increased. This is a significant environmental factor influencing half-life and an important consideration, given that cetirizine has been detected in wastewater and receiving waters from different locations globally.

Seasonal changes in antibiotics, antidepressants/psychiatric drugs, antihistamines and lipid regulators in a wastewater treatment plant.

Seasonal changes in the concentration of 21 pharmaceuticals in a wastewater treatment plant (WWTP) in Ceské Budejovice were investigated over 12months. The target compounds were 10 antibiotics, 4 antidepressants, 3 psychiatric drugs, 2 antihistamines and 2 lipid regulators. 272 Wastewater samples (136 influents and 136 effluents) were collected from March 2011 to February 2012 and analyzed using two-dimensional liquid chromatography coupled with tandem mass spectrometry. All studied pharmaceuticals were frequently detected in both the influent and the effluent wastewater samples, except for meclozine, which was only found in the influent. The mean concentration of pharmaceuticals varied from 0.006µgL(-1) to 1.48µgL(-1) in the influent and from 0.003µgL(-1) to 0.93µgL(-1) in the effluent. The concentration of most pharmaceuticals was higher during winter.

Simultaneous detection and quantification of select nitromusks, antimicrobial agent, and antihistamine in fish of grocery stores by gas chromatography-mass spectrometry.

Continually detected biologically persistent nitromusks; galaxolide (HHCB), tonalide (AHTN) and musk ketone (MK), antimicrobial triclosan (TCS), and antihistamine diphenhydramine (DPH) were examined for the first time in edible fillets originating from eight fish species grown in salt- and fresh-water. The sampled fish collected from local grocery stores were homogenized, extracted, pre-concentrated and analyzed by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM). The presence of the target compounds in fish extracts was confirmed based on similar mass spectral features and retention behavior with standards. Internal standard based calibration plots were used for quantification. The HHCB, AHTN, TCS and DPH were consistently observed with concentration of 0.163-0.892, 0.068-0.904, 0.189-1.182, and 0.942-7.472 ng g(-1), respectively. These values are at least 1-3 orders of magnitude lower than those obtained in environmental fish specimens. The MK was not detected in any fish.

Analysis of chlorpheniramine in human urine samples using dispersive liquid-liquid microextraction combined with high-performance liquid chromatography

A simple and environmentally friendly microextraction technique was used for determination of chlorpheniramine (CPM), an antihistamine drug, in human urine samples using dispersive liquid-liquid microextraction (DLLME) followed by high performance liquid chromatography with diode array detection (HPLC-DAD). In this extraction technique, an appropriate mixture of acetonitrile (disperser solvent) and carbon tetrachloride (extraction solvent) was rapidly injected into the urine sample containing the target analyte. Tiny droplets of extractant were formed and dispersed into the sample solution and then sedimented at the bottom of the conical test tube by centrifugation. Under optimal conditions, the calibration curve was linear in the range of 0.055-5.5 µg mL-1, with a detection limit of 16.5 ng mL-1. This proposed method was successfully applied to the analysis of real urine samples. Low consumption of toxic organic solvents, simplicity of operation, low cost and acceptable figures of merit are the main advantages of the proposed technique.

Utilizou-se uma técnica de microextração simples e ambientalmente amigável para a determinação de clorfeniramina (CPM), anti-histamínico, em amostras de urina humana, utilizando a microextração dispersiva líquido-líquido (DLLME), seguida por cromatografia líquida de alta eficiência com detecção por arranjo de diodos (HPLC-DAD). Nesse método de extração, mistura apropriada de acetonitrila (solvente dispersor) e tetracloreto de carbono (solvente de extração) foi injetada rapidamente na amostra de urina contendo o analito alvo. As pequenas gotículas de agente de extração foram formadas e dispersas na solução da amostra e, em seguida, sedimentadas no fundo do tubo cônico de ensaio por centrifugação. Em condições ótimas, a curva de calibração foi linear no intervalo entre 0,055 e 5,5 µg mL-1, com limite de detecção de 16,5 ng mL-1. O método proposto foi aplicado com sucesso na análise de amostras de urina reais. Baixo consumo de solventes orgânicos tóxicos, simplicidade de operação, baixo custo e figuras de mérito aceitáveis são as principais vantagens do método sugerido.