On-line Solid-phase Extraction Method Research Articles

The Ultratrace Determination of Fluoroquinolones in River Water Samples by an Online Solid-Phase Extraction Method Using a Molecularly Imprinted Polymer as a Selective Sorbent.

Fluoroquinolones (FQs) are broad-spectrum antibiotics widely used to treat animal and human infections. The use of FQs in these activities has increased the presence of antibiotics in wastewater and food, triggering antimicrobial resistance, which has severe consequences for human health. The detection of antibiotics residues in water and food samples has attracted much attention. Herein, we report the development of a highly sensitive online solid-phase extraction methodology based on a selective molecularly imprinted polymer (MIP) and fluorescent detection (HPLC-FLD) for the determination of FQs in water at low ng L−1 level concentration. Under the optimal conditions, good linearity was obtained ranging from 0.7 to 666 ng L−1 for 7 FQs, achieving limits of detection (LOD) in the low ng L−1 level and excellent precision. Recoveries ranged between 54 and 118% (RSD < 17%) for all the FQs tested. The method was applied to determining FQs in river water. These results demonstrated that the developed method is highly sensitive and selective.

Determination of trace organic contaminants by a novel mixed-mode online solid-phase extraction coupled to liquid chromatography–tandem mass spectrometry

In this study, a novel mixed-mode online solid-phase extraction (SPE) method was developed to recover miscellaneous trace organic contaminants (TrOCs) from environmental water samples. Six kinds of sorbents, including C18 substances, hypercross-linked polymers (2), cation-exchange resins, anion-exchange resins, and graphitized nonporous carbons, were packed into a single online SPE cartridge. Furthermore, a fully automated analytic method was established by coupling this mixed-mode online SPE with liquid chromatography tandem mass spectrometry (online SPE-LC-MS/MS). Sixty-nine TrOCs with diverse properties were selected to examine the performance of this mixed-mode SPE cartridge in comparison with solo-mode online SPE cartridges. The method quantification limit (MQL) and the relative recovery coefficient of TrOCs in diverse water matrices, including groundwater, surface water and sewage effluent were evaluated. The MQL of most TrOCs was lower than 10 ng L−1. The relative recovery coefficients for most TrOCs in the groundwater (50/69) and surface water (38/69) matrix fit in the satisfactory range. Moreover, mixed-mode online SPE coupled with LC-high-resolution MS was applied for a suspect screening of TrOCs in sewage effluents. A series of highly polar TrOCs that had scarcely been reported by previous studies were identified by this practical and easily accessible method. Finally, this novel mixed-mode online SPE with LC-MS/MS method was applied to quantify the TrOCs in the environmental water samples.

Determination of three urinary catecholamines and serotonin by on-line packed-fiber solid-phase extraction

生物单胺包括儿茶酚胺类以及5-羟色胺等,在中枢神经系统中扮演着非常关键的角色,也是临床上诊断神经内分泌肿瘤疾病的重要生物标志物。由于这类单胺类物质的强化学极性导致传统吸附材料对其吸附效果不佳,从复杂生物样本中同时检测更多的生物单胺存在挑战性。该文建立了一种基于聚冠醚纳米纤维在线固相萃取检测尿液中3种儿茶酚胺(多巴胺、肾上腺素、去甲肾上腺素)和5-羟色胺的方法。采用静电纺丝法制备聚二苯并-18-冠-6醚-聚苯乙烯复合纳米纤维(PCE-PS),制成装填纤维的固相萃取(PFSPE)柱,再将PFSPE柱与HPLC进行在线联用。该在线PFSPE-HPLC方法采用双三元泵进行样品富集净化和分析,左泵连接PFSPE柱,进行样品富集净化;右泵连接分析柱进行样品分离检测。控制切换阀的切换,实现样品富集后洗脱至分析柱中分离检测。结果表明,在线PFSPE-HPLC检测尿液儿茶酚胺(多巴胺、肾上腺素、去甲肾上腺素)和5-羟色胺在1~200 ng/mL范围内有良好的线性关系,线性相关系数达0.996以上。3种儿茶酚胺和5-羟色胺的检出限(S/N=3)分别为1和2.5 ng/mL,定量限(S/N=10)分别为2.5和5 ng/mL。空白尿液和实际尿液加标回收率在83.5%~117.7%之间,日内精密度<10%。PCE-PS复合纳米纤维在多次使用后无明显变化,具有良好的稳定性,可重复使用达95次以上。在线PFSPE-HPLC方法能够集样品在线前处理与分析检测于一体,省时省力,实现分析过程的高度自动化。该方法成功应用于尿液中3种儿茶酚胺和5-羟色胺的检测,可以为临床上相关疾病检测诊断和研究提供有力的技术支持。

Dithizone-functionalized C18 online solid-phase extraction-HPLC-ICP-MS for speciation of ultra-trace organic and inorganic mercury in cereals and environmental samples

A simple and efficient dithizone-functionalized solid-phase extraction (SPE) procedure, online coupled with high-performance liquid chromatography (HPLC)-inductively coupled plasma mass spectrometry, was developed for the first time for enrichment and determination of ultra-trace mercury (Hg) species (inorganic divalent Hg (Hg(II)), methylmercury (CH3Hg(II)) and ethylmercury (C2H5Hg(II)) in cereals and environmental samples. In the proposed method, functionalization of the commercial C18 column with dithizone, enrichment, and elution of the above Hg species can be completed online with the developed SPE device. A simple solution of 2-mercaptoethanol (1% (V/V)) could be used as an eluent for both the SPE and HPLC separation of Hg species, significantly simplifying the method and instrumentation. The online SPE method was optimized by varying dithizone dose, 2-mercaptoethanol concentration, and sample volume. In addition, the effect of pH, coexisting interfering ions, and salt effect on the enrichment was also discussed. Under the optimized conditions, the detection limits of Hg species for 5 mL water sample were 0.15 ng/L for Hg(II), 0.07 ng/L for CH3Hg(II), and 0.04 ng/L for C2H5Hg(II) with recoveries in the range of 85%–100%. The developed dithizone-functionalized C18 SPE column can be reused after a single functionalization, which significantly simplifies the enrichment step. Moreover, the stability of Hg species enriched on the SPE column demonstrated its suitability for field sampling of Hg species for later laboratory analysis. This environment-friendly method offers a robust tool to detect ultra-trace Hg species in cereals and environmental samples.

A reciprocating magnetic field assisted on-line solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry determination of trace tetracyclines in water

A reciprocating magnetic-field-assisted on-line solid-phase extraction (RMF-SPE) method coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for continuous enrichment of trace chemicals in water samples. Under the assist of the reciprocating magnetic field, carboxyl-modified magnetic nanoparticles (CMNPs) were applied to prepare microcolumn with even dispersion by periodical motion, instead of traditional compaction as extraction sorbents. When water sample passed through the extraction region, dynamic sorbents generates an advantage of countless contacts between sorbents and targets without blocking for high efficient extraction. In this study, the on-line RMF-SPE method was established and evaluated by determination of tetracyclines (TCs) from water samples as analysis models, including oxytetracycline, tetracycline, demeclocycline, metacycline, chlortetracycline, and doxycycline. Experimental conditions have been investigated such as flow rate, reciprocating speed, elution time, and so on. The method showed high relative recovery (95.4–111.1%) and good repeatability with RSD from 2.9 to 11.8% for the 200 mL water sample. The linearity range, limits of detection (LODs), and limits of quantification (LOQs) were 0.5–200 μg L−1 (chlortetracycline) and 0.1–200 μg L−1 (other TCs), 12.0–74.1 ng L−1, and 40.1–247 ng L−1, respectively. More importantly, the high enrichment factors in a range of 204 (chlortetracycline) to 276 (demeclocycline) indicate that a small amount of dynamic sorbents (only 10 mg) give full play to extraction attributing to the reciprocating movement, especially for trace analysis and continuous extraction, which is significant for water samples from sea, river and domestic waste.

Stanozolol-N-glucuronide metabolites in human urine samples as suitable targets in terms of routine anti-doping analysis.

The exogenous anabolic-androgenic steroid (AAS) stanozolol stays one of the most detected substances in professional sports. Its detection is a fundamental part of doping analysis, and the analysis of this steroid has been intensively investigated for a long time. This contribution to the detection of stanozolol doping describes for the first time the unambiguous proof for the existence of 17-epistanozolol-1'N-glucuronide and 17-epistanozolol-2'N-glucuronide in stanozolol-positive human urine samples due to the access to high-quality reference standards. Examination of excretion study samples shows large detection windows for the phase-II metabolites stanozolol-1'N-glucuronide and 17-epistanozolol-1'N-glucuronide up to 12 days and respectively up to almost 28 days. In addition, we present appropriate validation parameters for the analysis of these metabolites using a fully automatic method online solid-phase extraction (SPE) method already published before. Limits of identification (LOIs) as low as 100 pg/ml and other validation parameters like accuracy, precision, sensitivity, robustness, and linearity are given.

Automated separation and measurement of 226Ra and trace metals in freshwater, seawater and fracking water by online ion exchange chromatography coupled with ICP-MS

An online solid-phase extraction method combined with ICP-MS was developed to separate and quantify low levels of 226Ra and other metals in drinking water, lake, river and sea water, and fracking fluids. A dual-column lab-on-valve and multi-syringe flow injection analysis (LOV-MSFIA) system was developed to provide precise measurement of 226Ra in samples with total dissolved solids (TDS) less than 2%. For samples with higher levels of TDS (up to 20%), a triple-column LOV-MSFIA system was developed, which used AG 50 W-X8 cation exchange, Sr spec andNobias Chelate resins. Compared to earlier automated systems for Ra analysis, the dual and triple column systems described here were optimized to accommodate smaller sample volumes, more precise flow control and lower limits of detection (LOD). The LOV-MSFIA system coupled with ICP-MS is a significant improvement over traditional methods for low level 226Ra measurements, which require extended sample holding and/or analysis time. External calibration and standard addition were used to quantify the concentration of Ra for the LOV-MSFIA system. After method optimization, LODs for 226Ra as low as 4.3 mBq L−1 (1.75 fg L−1) were obtained in different sample matrices. The concentrations of selected metals were also measured on the triple-column system, together with Ra, with a total online processing time of 28.5 min per sample. Thus, the online LOV-MSFIA system is shown to be a powerful tool for the rapid analysis of low levels of 226Ra, as well as other metals, in various types of aqueous samples.

Stability Indicating Method for Polysorbate 80 in Protein Formulations.

Polysorbates (also known as "Tween") are common components of protein formulations used to minimize protein adsorption and stabilize the protein. These nonionic surfactants are heterogenous mixtures of fatty acids with a complex reversed-phase profile due to the inhomogeneity of the polymers present. Polysorbates can be oxidized, which can be hard to detect in the complex polymer profile. Further adding to the analytical challenge is the lack of a chromophore for the detection of these polymers. The routine analysis of polysorbates in protein formulations was greatly improved through the introduction of online solid-phase extraction (SPE) to simplify the polysorbate profile for quantification. However, this method combines many of the polysorbate polymers into a single peak for detection, thus limiting its effectiveness for detecting degradation. To address the need for a stability indicating method without the complexity of the reversed-phase profile, an optimized online SPE method was developed and investigated. Using polysorbate 80, this investigation shows that further expanding the step gradient can yield a profile that is stability indicating and available for routine testing of protein formulation.

Simple determination of six groups of lipophilic marine algal toxins in seawater by automated on-line solid phase extraction coupled to liquid chromatography-tandem mass spectrometry

Lipophilic marine algal toxins (LMATs) are highly toxic secondary metabolites produced by marine microalgae that pose a great threat to marine aquaculture organisms and human health. In this study, a novel and automated method for the simultaneous determination of six groups of LMATs in seawater was developed by on-line solid phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Condition optimization and method validation were performed, and the recoveries of all 14 target LMATs featuring different properties ranged from 83.5% to 96.0%. The limits of detection of most target compounds were within ≤3.000 ng/L with good precision (relative standard deviation ≤ 12.1%) and linearity (R2≥0.9916). Compared with off-line SPE methods, the proposed on-line SPE method has better recovery, sensitivity, repeatability, and throughput; in addition, the volume of seawater sample necessary to conduct determinations is greatly reduced in the present method. Finally, the method was applied to determine LMATs in actual seawater samples collected from the Bohai and South Yellow Seas of China in summer, and okadaic acid and pectenotoxin-2 were detected in all seawater samples. The highest concentration of ∑LMATs (22.23 ng/L) occurred in the coastal mariculture area of Shandong Province. Therefore, routine monitoring of LMATs in seawater of the coastal mariculture zone is necessary to prevent shellfish contamination especially in summer, and the proposed on-line SPE-LC-MS/MS method is a powerful way for direct and automatic detection of various LMATs in coastal mariculture area.

Comprehensive analysis of synthetic cannabinoids and metabolites in oral fluid by online solid-phase extraction coupled to liquid chromatography-triple quadrupole-mass spectrometry.

The class of novel psychoactive substances known as synthetic cannabinoids (SC) includes illicit compounds that are sprayed on plant material and smoked or sold as liquids to be vaporized in e-cigarettes. In toxicological analysis of SC, fast analytical methods are needed for the detection and confirmation of parent drugs and metabolites at very low levels. While various analytical methods have been developed for SC in blood and urine, few are available for alternative matrices such as oral fluid (OF). There are numerous advantages to using OF as a sample matrix for SC analysis, including non-invasive collection, lesser risk of adulteration, and presence of both parent drug and metabolites. Here we report a validated online solid-phase extraction (online SPE) method coupled to LC-QqQ-MS for rapid confirmation and quantitation of 72 structurally diverse SC parent drugs and metabolites in OF with 2.5min of preconcentration time and a total elution time of < 10min. The use of online SPE for sample pretreatment facilitates rapid and consistent processing and greatly increases sample throughput. The method was fully validated according to relevant guidelines (ANSI/ASB Standard 036). Bias and precision values were within ± 20% for all compounds in human OF matrix. Method detection and quantitation limits ranged from 0.4 to 3.8ng/mL and from 1.1 to 11.6ng/mL, respectively. Recovery, matrix effects, process efficiency, carryover, and stability were also within acceptable limits for the majority of compounds. Successful application of the method was demonstrated using blank human OF fortified with SC in addition to a set of authentic OF specimens previously tested by another laboratory. Graphical abstract.

Mass spectrometric quantification of urinary 6-sulfatoxymelatonin: age-dependent excretion and biological variation.

Regulators of circadian rhythm, including melatonin, influence fundamental biological processes. Measuring the melatonin metabolite 6-sulfatoxymelatonin in urine can estimate melatonin production. 6-sulfatoxymelatonin is mainly analyzed by immunoassays, but these methods are hampered by cross-reactivity and poor reproducibility when used to analyze small molecules. Therefore, we validated a high-throughput liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to quantify 6-sulfatoxymelatonin in urine. We evaluated age-dependent 24-h excretion of 6-sulfatoxymelatonin into urine and the biological variation of urinary excretion in healthy individuals. The online solid phase extraction method combined with LC-MS/MS was validated according to international guidelines, and used to measure the excretion of 6-sulfatoxymelatonin into urine of 240 healthy individuals. Biological variation of 6-sulfatoxymelatonin excretion was examined in 10 healthy individuals. Urinary 6-sulfatoxymelatonin results were well within the validation criteria (interassay coefficient of variation:<5.4%, quantification limit: 0.2nmol/L). There was an age-related decrease in 6-sulfatoxymelatonin excretion into 24-h urine [F(5, 234)=13.9; p<0.001]. Within-subject variation of 6-sulfatoxymelatonin was 39.2% in day urine, 15.1% in night urine, and 12.2% in 24-h urine. Between-subject variation was 39.1% in day urine, 37.9% in night urine, and 36.8% in 24-h urine. This MS-based method enables straightforward, reproducible, and sensitive quantification of 6-sulfatoxymelatonin in urine. Urinary 6-sulfatoxymelatonin levels decreased with age. Biological variation of 6-sulfatoxymelatonin excretion into urine was high between subjects and lower within subjects, indicating that repeated measurements of 6-sulfatoxymelatonin in 24-h urine are needed in future studies.

Development and validation of a simple online-SPE method coupled to high-resolution mass spectrometry for the analysis of stanozolol-N-glucuronides in urine samples.

Stanozolol is still the most commonly used illicit anabolic-androgenic steroid (AAS) in professional sports. Therefore, accurate and fast analysis and long detection windows are of great interest in the field of antidoping analysis. In this work, a very simple, fast, and highly sensitive online solid-phase extraction method coupled with liquid chromatography-high-resolution tandem mass spectrometry (HPLC-HRMSMS) for the analysis of stanozolol-N-glucuronides was developed. This fully validated procedure is characterized by only a few manual steps (dilution and addition of internal standard) in the sample preparation. A limit of identification (LOI) of 75 pg/mL, high accuracy (87.1%-102.1%), precision (3.1%-7.8%), and sensitivity was achieved. Furthermore, good linearity (> 0.99) and robustness, as well as no carry-over effects, could be observed. In addition to excellent confirmation analysis performance, this method shows sufficient potential for the identification and characterization of unknown metabolites. Using this method, it was possible to unambiguously confirm the presence of 1'N- and 2'N-stanozolol-glucuronide in human urine for the first time due to the access to reference material.

Amino-modified Scholl-coupling mesoporous polymer for online solid-phase extraction of plant growth regulators from bean sprouts

A new amino-modified Scholl-coupling mesoporous polymer (NH2@SMPA)-online solid-phase extraction method, coupled with high-performance liquid chromatography (online SPE-HPLC) was established for the analysis of six plant growth regulators (PGRs) in bean sprouts. NH2@SMPA was synthesized by acid-catalyzed deacetylation of acetylamino-Scholl-coupling mesoporous polymer (SMPA). The diversity of functional groups, such as aromatic, acetylamino, and NH2, was conducive to multiple binding interactions between NH2@SMPA and PGRs. NH2@SMPA exhibited superior extraction capability for PGRs, compared with SMPA and commercial adsorbents. The extraction conditions, including loading solvent, pH of loading solution, eluting solvent, and flow rates of loading and elution, were optimized. Under the optimized conditions, wide linear ranges (0.01–500 μg kg−1) and low detection limits (2.34–20.2 ng kg−1) were obtained. The recoveries were satisfactory, i.e., 86.0% to 109% with relative standard deviations ≤9.8% (n = 3). Finally, the online SPE-HPLC method was successfully used for determination of PGRs in bean sprouts.

A retrospective and prospective of the use of bio- and nanomaterials for preconcentration, speciation, and determination of trace elements: a review spanning 25years of research.

This review covers the investigations carried out with my colleagues and students during the last 25years aimed at the development of analytical procedures for the preconcentration and/or speciation analysis of trace and ultra-trace elements using bio- and nanosorbents employing different methodologies, analytical techniques, and instrumental approaches. In the last years, an important part of this research was based on the use of nanomaterials for preconcentration and/or speciation studies. For their properties, they constitute a break point in the evolution of analytical chemistry. Special attention was paid to carbon nanotubes (CNTs) that resulted effective sorbents in flow systems using different immobilization strategies to improve their sorption capabilities. They resulted unique tools for on-line solid-phase (micro)extraction methods providing the appropriate selectivity (clean-up) and sensitivity (preconcentration) to reach the expected levels of many elements in matrices of biological or environmental interest. The performance of the different substrates, their strengths and weaknesses for the determination of trace elements, and their species in different matrices by a variety of analytical techniques are discussed in detail, along with perspectives and possible challenges in future development. This survey contains 96 references and covers primarily the literature published over the last 25years by our research group. Relevant publications on the topics discussed were also included.

Автоматизированный синтез [&lt;sup&gt;18&lt;/sup&gt;F]фторметилхолина, радиофармпрепарата для позитронной эмиссионной томографии

Разработана автоматизированная технология синтеза [18F]фторметилхолина, радиофармпрепарата для диагностики онкологических заболеваний методом позитронной эмиссионной томографии. Синтез был выполнен на стационарном модуле TracerLab FXFN (GE Healthcare) по технологии, основанной на комбинированном использовании процессов on-line алкилирования и методов твердофазной экстракции. Модуль синтеза был модернизирован, что позволило оперировать разными значениями потоков гелия на критичных стадиях процесса. Радиохимический выход [18F]фторметилхолина составил более 10 %, что достаточно для получения нескольких клинических доз. Параметры контроля качества полученного [18F]фторметилхолина удовлетворяют требованиям фармакопеи РФ.

Automated on-line SPE determination of amisulpride in human plasma using LC coupled with restricted-access media column

An automated on-line solid-phase extraction (SPE) method coupled with high performance liquid chromatography (HPLC) was developed for the first application to rapid quantification of trace amisulpride in human plasma. A kind of restricted-access media (RAM) column (Capcell Pak MF Ph-1) was adopted for highly efficient extraction of amisulpride and meanwhile for the limited access of macromolecular matrices. It was robust and reusable for >1000 times. The utilization of two programmable pumps enabled the simultaneous execution of SPE and HPLC analysis within 10 min. Additionally, using appropriate valve-switching time was found to efficiently reduce the contamination of HPLC system caused by co-elution of impurity from an RAM column, facilitating continuous analysis of large-scale samples. The method was characterized by free of internal standard (IS), which exhibited low limit of detection (0.0035 μg·mL−1), satisfactory precision and accuracy (recoveries of 98.1%–104.6% with relative standard deviations below 4.6%). Amisulpride was successfully detected in the plasma samples originated from four patients. Notably, interindividual differences of plasma sample matrices did not yield an adverse effect on the accuracy of our IS-free method. The comparison to previous methods shows the superiority of the method in terms of sensitivity, IS requirement, speed, and automation. Thus, the method has great potential for the application to therapeutic drug monitoring as well as large-scale bioanalytical and clinical studies.

Multi-residue analysis of sulfonamide antibiotics in honey samples by on-line solid phase extraction using molecularly imprinted polymers coupled to liquid chromatography-tandem mass spectrometry

This work reports the development of a sensitive and automated online solid phase extraction method using molecularly imprinted polymers (MISPE) coupled to high performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) (HPLC), for the identification and quantification of six sulfonamide antibiotics, namely sulfapiridyne, sulfadoxine, sulfaquinoxaline, sulfacetamide, sulfachloropyridazine and sulfamonomethoxine in honey samples from the Cuban market. The samples were hydrolyzed in acidic media to release the sugar-bound sulfonamides before injection into the preconcentration system. Polymer composition was selected using a combinatorial approach. Several parameters affecting the performance of the MISPE method were optimized to reduce nonspecific binding with the non-imprinted polymer and achieve a selective rebinding of the target antimicrobials. Method validation was performed according to Commission Decision 2002/657/EC in terms of linearity, recoveries, precision, specificity, decision limit (CCα) and detection capability (CCβ). Intraday recoveries at three concentration levels (1, 10 and 20 μg Kg-1) were between 84.3 and 104.7% (RSD < 11.6%) while interday average recoveries were in the ranges 65.5–119.3% (RSDs < 10.4%). The values of CCα and CCβ values were in the ranges 0.1–4.2 and 0.2–4.4 μg kg−1, respectively. The limits of detection and quantitation for the investigated sulfonamides ranged from 0.004–1.050 µg kg−1 and 0.014–3.499 µg kg−1, respectively. The method described has been applied to the analysis of honey samples from Cuban producers.

Measurement of apixaban, dabigatran, edoxaban and rivaroxaban in human plasma using automated online solid-phase extraction combined with ultra-performance liquid chromatography-tandem mass spectrometry and its comparison with coagulation assays

BackgroundMeasurement of direct oral anticoagulants (DOACs) concentration in patient blood is essential in special clinical circumstances. MethodsWe developed a fast, selective and sensitive method for simultaneous measurement of DOACs in human plasma consisting of an automated online solid-phase extraction method coupled with ultra-performance liquid chromatography electrospray ionization-tandem mass spectrometry (online SPE-UPLC-MS/MS). ResultsThe calibration curves of all DOACs were linear over the working range (apixaban: 0.25–760 μg/L, r > 0.99; dabigatran: 0.5–900 μg/L, r > 0.99; edoxaban: 0.6–800 μg/L, r > 0.99; rivaroxaban: 0.5–900 μg/L, r > 0.99). Limits of detection in the plasma matrix were < 0.2 μg/L, whereas the lower limits of quantification were < 0.6 μg/L for all DOACs. The intraassay and interassay CV for all DOACs were < 6%. Mean recoveries were between 61.4% and 91.6%. Method comparison between our online SPE-UPLC-MS/MS assay and commercially available functional based coagulation assays using patient samples showed a high degree of correlation for all investigated DOACs. ConclusionsWe developed and validated the first online SPE-UPLC-MS/MS method for fast, sensitive, specific, and reliable measurement of the new generation of DOACs and compared this method with commercial available coagulation assays.

Quantitative determination of risperidone, paliperidone and olanzapine in human serum by liquid chromatography-tandem mass spectrometry coupled with on-line solid-phase extraction.

A recent guideline recommends therapeutic drug monitoring for risperidone, paliperidone and olanzapine, which are frequently used second-generation antipsychotics. We developed a simple high-performance liquid chromatography-tandem mass spectrometry coupled with an online solid-phase extraction method that can be used to measure risperidone, paliperidone and olanzapine using small (40 μL) samples. The analytes were extracted from serum samples automatically pre-concentrated and purified by C8 (5 μm, 2.1 × 30 mm) solid-phase extraction cartridges, then chromatographed on an Xbidge™ C18 column (3.5 μm, 100 × 2.1 mm) thermostatted at 30°C with a mobile phase consisting of 70% acetonitrile and 30% ammonium hydroxide 1% solution at an isocratic flow rate of 0.3 mL/min, and detected with tandem mass spectrometry. The assay was validated in the concentration range from 2.5 to 160 ng/mL. Intra- and inter-day precision for all analytes was between 1.1 and 8.2%; method accuracy was between 6.6 and 7.6%. The risperidone and paliperidone assay was compared with a high-performance liquid chromatography-ultraviolet assay currently used in our hospital for risperidone and paliperidone therapeutic drug monitoring, and the results of weighted Deming regression analysis showed good agreement. For the olanzapine assay, we compared 20 samples in separate re-assays on different days; all the relative errors were within the 20% recommended limit.

On-line solid-phase extraction method for determination of triazine herbicides and degradation products in seawater by ultra-pressure liquid chromatography–tandem mass spectrometry

A fast, simple, selective and sensitive method has been developed for the determination of nine triazine herbicides (ametryn, atrazine, cyanazine, prometryn, propazine, simazine, simetryn, terbuthylazine and terbutryn) and eight degradation products (desethyl atrazine, desethyl-desisopropyl atrazine, desethyl 2-hydroxyatrazine, desethyl terbuthylazine, desisopropyl atrazine, desisopropyl 2-hydroxyatrazine, 2-hydroxyatrazine and 2-hidroxyterbuthylazine) in seawater samples. On-line solid-phase extraction coupled with ultra-pressure liquid chromatography-tandem mass spectrometry was employed for simultaneous analysis of all compounds in 11min. Validation parameters were studied through the estimation of the limits of detection and quantification, calibration curves and precision. Limits of quantification ranged from 0.023 to 0.657μgL−1. Good linearity was obtained for all compounds with R2>0.99 in all cases. Furthermore, inter-day precision (0–2.1%) and intra-day precision (0–3.9%) were shown to be satisfactory. On-line solid-phase extraction recoveries in spiked unpolluted seawater sample were evaluated and acceptable values (80.3–99.8%) with adequate RSD (0.1–3.1%) were found.Finally, the proposed method was applied to the analysis of the target compounds in seawater samples collected from seawater nearby a zone of intensive horticulture of Matosinhos (Portugal). The concentrations of the herbicides were below the limit of detection in all cases.