Enhanced Chemoradiotherapy for MRSA-Infected Osteomyelitis Using Immunomodulatory Polymer-Reinforced Nanotherapeutics.

The eradication of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge due to its development of biofilm-induced antibiotic resistance and impaired innate immunity, which often leads to frequent surgical failure. Here, the design, synthesis, and performance of X-ray-activated polymer-reinforced nanotherapeutics that modulate the immunological properties of infectious microenvironments to enhance chemoradiotherapy against multidrug-resistant bacterial deep-tissue infections are reported. Upon X-ray radiation, the proposed polymer-reinforced nanotherapeutic generates reactive oxygen species and reactive nitrogen species. To robustly eradicate MRSA biofilms at deep infection sites, these species can specifically bind to MRSA and penetrate biofilms for enhanced chemoradiotherapy treatment. X-ray-activated nanotherapeutics modulate the innate immunity of macrophages to prevent the recurrence of osteomyelitis. The remarkable anti-infection effects of these nanotherapeutics are validated using a rat osteomyelitis model. This study demonstrates the significant potential of a synergistic chemoradiotherapy and immunotherapy method for treating MRSA biofilm-infected osteomyelitis.

Thermosensitive Nanotherapeutics for Localized Photothermal Ablation of MRSA-Infected Osteomyelitis Combined with Chemotherapy.

Chronic osteomyelitis is an inflammatory skeletal disease caused by a bacterial infection that affects the periosteum, bone, and bone marrow. Methicillin-resistant Staphylococcus aureus (MRSA) is the most common causative agent. The bacterial biofilm formed on the necrotic bone is a considerable challenge to treating MRSA-infected osteomyelitis. Here, we developed an all-in-one cationic thermosensitive nanotherapeutic (TLCA) for treating MRSA-infected osteomyelitis. The prepared TLCA particles were positively charged and <230 nm in size, which allowed them to diffuse effectively into the biofilm. The positive charges of the nanotherapeutic accurately targeted the biofilm, and it subsequently regulated the drug release under near-infrared (NIR) light irradiation, thereby efficiently exerting the synergistic effect of NIR light-driven photothermal sterilization and chemotherapy. More than 80% of the antibiotics were abruptly released at 50 °C, which dispersed the biofilm by up to 90%. When applied to MRSA-infected osteomyelitis, with a localized temperature of 50 °C induced by 808 nm laser irradiation, it not only eliminated the bacteria and controlled infection but also inhibited the bone tissue inflammatory response, significantly reducing TNF-α, IL-1ß, and IL-6 levels. In conclusion, we constructed an all-in-one antimicrobial treatment modality that provides a new and effective strategy for the topical treatment of chronic osteomyelitis.

Guanidinium-Decorated Nanostructure for Precision Sonodynamic-Catalytic Therapy of MRSA-Infected Osteomyelitis.

Osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilm infection is difficult to eradicate and can even be life-threatening. Given that the infection is persistent and deep-seated in the bone tissue, controlled and efficient treatment of osteomyelitis remains challenging. Herein, an activatable nanostructure (Au/TNT@PG) is presented for synergistic sonodynamic-catalytic therapy of MRSA-infected osteomyelitis. The Au/TNT@PG backbone is obtained by conjugating a guanidinium-rich polymer (PG), a component that penetrates the biofilm matrix, onto ultrasound (US)-absorbing gold-doped titanate nanotubes (Au/TNTs). Under deep-penetrating US irradiation, the nanocomposite generates 1 O2 for sonodynamic therapy and catalyzes the decomposition of endogenous H2 O2 into toxic •OH in the acidic infection microenvironment for catalytic therapy, leading to bacterial cell death. Its robust antibacterial effectiveness is attributable to its bacteria-capturing ability, the biofilm penetrability of positively charged guanidinium, and the subsequent synergistic effect of sonodynamic-catalytic action of Au/TNT. Such a remotely controlled approach potentiates the polarization of macrophages to M2-type while suppressing the M1-type, leading to topical inflammation resolution and enhanced osteoblast proliferation and differentiation to inhibit bone loss. Therefore, this study provides a generic nanotherapeutic approach for efficient sonodynamic-catalytic therapy with respect to osteomyelitis.

NIR-activated nanosystems with self-modulated bacteria targeting for enhanced biofilm eradication and caries prevention.

The efficacious delivery of antimicrobial drugs to intractable oral biofilms remains a challenge due to inadequate biofilm penetration and lack of pathogen targeting. Herein, we have developed a microenvironment-activated poly(ethylene glycol) (PEG)-sheddable nanoplatform to mediate targeted delivery of drugs into oral biofilms for the efficient prevention of dental caries. The PEGylated nanoplatform with enhanced biofilm penetration is capable of deshielding the PEG layer under slightly acidic conditions in a PEG chain length-dependent manner to re-expose the bacteria-targeting ligands, thereby facilitating targeted codelivery of ciprofloxacin (CIP) and IR780 to the bacteria after accumulation within biofilms. The nanoplatform tends to induce bacterial agglomeration and suffers from degradation in the acidic oral biofilm microenvironment, triggering rapid drug release on demand around bacterial cells. The self-modulating nanoplatform under near-infrared (NIR) irradiation accordingly displays greatly augmented potency in oral biofilm penetration and disruption compared with drugs alone. Topical oral treatment with nanoplatforms involving synergetic pharmacological and photothermal/photodynamic trinary therapy results in robust biofilm dispersion and efficacious suppression of severe tooth decay in rats. This versatile nanoplatform can promote local accumulation and specific drug transport into biofilms and represents a new paradigm for targeted drug delivery for the management of oral biofilm-associated infections.

Synergy between Clinical Microenvironment Targeted Nanoplatform and Near-Infrared Light Irradiation for Managing Pseudomonas aeruginosa Infections.

Chronic infections caused by Pseudomonas aeruginosa pose severe threats to human health. Traditional antibiotic therapy has lost its total supremacy in this battle. Here, nanoplatforms activated by the clinical microenvironment are developed to treat P. aeruginosa infection on the basis of dynamic borate ester bonds. In this design, the nanoplatforms expose targeted groups for bacterial capture after activation by an acidic infection microenvironment, resulting in directional transport delivery of the payload to bacteria. Subsequently, the production of hyperpyrexia and reactive oxygen species enhances antibacterial efficacy without systemic toxicity. Such a formulation with a diameter less than 200 nm can eliminate biofilm up to 75%, downregulate the level of cytokines, and finally promote lung repair. Collectively, the biomimetic design with phototherapy killing capability has the potential to be an alternative strategy against chronic infections caused by P. aeruginosa.

Glycosylated Nanotherapeutics with ß-Lactamase Reversible Competitive Inhibitory Activity Reinvigorates Antibiotics against Gram-Negative Bacteria.

Antibiotics are currently first-line therapy for bacterial infections. However, the curative effect of antibiotic remedies is limited due to increasingly prevalent bacterial resistance. The strategy to reverse intrinsic acquired drug resistance presents a promising option for reinvigorating antibiotic therapy. Here, we developed a ß-lactamase-inhibiting macromolecule composed of benzoxaborole and dextran for precise transport of ß-lactam antibiotics to strains overexpressing ß-lactamase. Benzoxaborole-derived nanotherapeutics enabled specific recognition and rapid internalization, and the nanotherapeutics with a high affinity toward bacteria distinctly inhibited the catalytic activity of bacterially secreted ß-lactamase by a reversible competitive mechanism. Thus, the system entrapping cefoxitin harbored a significantly enhanced ability to kill drug-resistant Escherichia coli compared to the ability of the drug by specifically overcoming the membrane barrier and acquired resistance mechanism of ß-lactamase overproduction. The reversible competitive nanotherapeutics exhibited a robust therapeutic efficacy in rat wounds infected with drug-resistant bacteria; the efficacy was due to efficient bacterial elimination and collateral benzoxaborole-dependent amelioration of the inflammatory response. The above results offered insights into the facile design of precise macromolecular adjuvants to exclusively reverse the acquired bacterial resistance mechanism and increase the utility of antibiotic therapies against antibiotic-resistant bacterial infections.

An epicardial delivery of nitroglycerine by active hydraulic ventricular support drug delivery system improves cardiac function in a rat model.

We have used a novel active hydraulic ventricular support drug delivery system (ASD) device, which is a non-transplant surgical approach, can adhere to heart surface, and deliver the drug directly into the epicardium. This study is intended to compare the effect of administration of nitroglycerine (NTG) through ASD and intravenous injection on the ischemic injury during acute myocardial infarction (AMI). 30 male SD rats were allocated into five groups (n = 6): sham, AMI, I.V., ASD high dose (ASDH), and ASD low dose (ASDL) respectively. Ligation of the left anterior descending (LAD) coronary artery was performed to induce myocardial infarction. Electrocardiograms were monitored, and serum myoglobin (Mb) was assessed. Hemodynamics was observed on pre- and post-operation. Hematoxylin and eosin (H&E) staining was performed for histological diagnosis. In all model animals, ligation of LAD provoked ST segment elevation and Mb level augmentation. In ASDH group, Mb showed obvious decrease as compared with other treatment groups. Hemodynamic parameters showed significant improvement in ASDH and ASDL groups than the I.V. group. H&E staining showed that AMI group rats had wavy fibers and loss of transverse striations while ASD group rats had obvious improvement. Unlike the I.V. group, ASD group rats showed significant vasodilation. Therefore, delivery of NTG through ASD to the cardiomyocytes could improve the therapeutic efficacy. A novel effective route for local delivery of agents to manage AMI has been proved.

Novel Treatment of Experimental Autoimmune Prostatitis by Nanoparticle-Conjugated Autoantigen Peptide T2.

The exact etiology and pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still unknown, as a result, available therapeutic options for patients are far from satisfactory. Therefore, there is a need to develop a valid therapeutic approach that can ameliorate the manifestations of CP/CPPS. Fifty male C57BL/6 mice were randomly divided into five groups of ten mice each. All groups except naïve were subcutaneously injected with 0.2 ml of T2 plus complete Freund adjuvant (CFA) on day 0 and 14 to generate valid CP/CPPS model. After successful CP/CPPS induction, model group was injected with 0.2 ml of normal saline while PLGA, PLGA-OVA, and PLGA-T2 groups were administered intravenously with 0.2 ml mixture of PLGA, PLGA-OVA, and PLGA-T2, respectively. Voiding behavior, pain threshold, and hematoxylin and eosin staining were used to assess micturition habits, pain intensity as well as prostate inflammation. Additionally, TNF-α, CRP, and IL-10 levels in plasma were measured by using ELISA kits. Mice administered with PLGA-T2 showed higher pain threshold, lower urine frequencies, mild edema, and inflammation in prostate tissue in comparison to other groups. Moreover, the expression of TNF-α and CRP levels was markedly decreased while IL-10 expression was increased in the PLGA-T2 treatment group as compared to the other groups. Our results showed that nanoparticles conjugated with autoantigen novel peptide T2 could successfully alleviate or even heal CP/CPPS to some extent in mice. This study provides an easy, useful, and economic tool for ameliorating the manifestations of CP/CPPS that will improve the therapeutic approaches.

A nanoparticle-coupled T2 peptide induces immune tolerance and ameliorates chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in mice model.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease of unclear etiology. Precise treatment of CP/CPPS is not available due to lack of specific cause; however, autoimmunity is the most valid theory. We develop a new treatment strategy that involves synthesis and coupling of biodegradable nanoparticles to antigenic T2 peptide to induce immune tolerance in CP/CPPS mice models. A total of 50 male C57BL/6 mice were randomized into five groups, that is, naïve, Model, PLGA-PEMA, PLGA-PEMA-OVA323-339 , and PLGA-PEMA-T2 group. All groups except naïve were injected subcutaneously on day 0 with 0.2 mL of T2 peptide with CFA to generate valid CP/CPPS models. After successful induction of CP/CPPS, Model group, PLGA-PEMA, PLGA-PEMA-OVA, and PLGA-PEMA-T2 groups were treated with 0.15 mL of normal saline, 0.2 mg of PLGA-PEMA and PLG-PEMA-T2 and 0.3 mg PLGA-PEMA-OVA nanoparticles, respectively, on day 28. Hematoxylin and eosin staining, and ELISA were used to evaluate the variation in CP/CPPS manifestations and seral level of IL-10 in each group. Pain threshold and voiding behavior were also recorded for every group. Mice treated with PLGA-PEMA-T2 exhibited enhanced pain threshold, reduced urine frequency, and prostate pathology. Furthermore, serum level of inflammatory mediators (TNF-α and CRP) were reduced and anti-inflammatory IL-10 was enhanced in PLGA-PEMA-T2 group as compared to other groups. Our results demonstrate that PLGA-PEMA-T2 nanoparticle ameliorates disease manifestations in CP/CPPS mice models and upregulates IL-10 which is essential for tolerance induction. This strategy highlights the new therapeutic approach utilizing biodegradable nanoparticles for the treatment of CP/CPPS.

Role of oxidative stress in pathology of chronic prostatitis/chronic pelvic pain syndrome and male infertility and antioxidants function in ameliorating oxidative stress.

Oxidative stress (OS) is a result of the imbalance between reactive oxygen species (ROS) and antioxidants in the body that can cause tissue damage. Oxidative stress has a significant involvement in the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and male infertility. CP/CPPS is a major risk factor for male infertility due to generation of excessive ROS that damage sperm DNA, lipids, and proteins, resulting in compromised vitality and decreased sperm motility. Here we present a comprehensive review of oxidative stress relevance in CP/CPPS and male infertility, and embody the protective effects of antioxidants against ROS. An online literature was searched using the following keywords/terms: oxidative stress, ROS, Oxidative stress and chronic prostatitis, oxidative stress and male infertility and antioxidants. Original and review articles, clinical trials, and case reports of human and animal studies published till 2017 were searched using the PubMed and MEDLINE.

The promising future of ventricular restraint therapy for the management of end-stage heart failure.

Complicated pathophysiological syndrome associated with irregular functioning of the heart leading to insufficient blood supply to the organs is linked to congestive heart failure (CHF) which is the leading cause of death in developed countries. Numerous factors can add to heart failure (HF) pathogenesis, including myocardial infarction (MI), genetic factors, coronary artery disease (CAD), ischemia or hypertension. Presently, most of the therapies against CHF cause modest symptom relief but incapable of giving significant recovery for long-term survival outcomes. Unfortunately, there is no effective treatment of HF except cardiac transplantation but genetic variations, tissue mismatch, differences in certain immune response and socioeconomic crisis are some major concern with cardiac transplantation, suggested an alternate bridge to transplant (BTT) or destination therapies (DT). Ventricular restraint therapy (VRT) is a promising, non-transplant surgical treatment wherein the overall goal is to wrap the dilated heart with prosthetic material to mechanically restrain the heart at end-diastole, stop extra remodeling, and thereby ultimately improve patient symptoms, ventricular function and survival. Ventricular restraint devices (VRDs) are developed to treat end-stage HF and BTT, including the CorCap cardiac support device (CSD) (CSD; Acorn Cardiovascular Inc, St Paul, Minn), Paracor HeartNet (Paracor Medical, Sunnyvale, Calif), QVR (Polyzen Inc, Apex, NC) and ASD (ASD, X. Zhou). An overview of 4 restraint devices, with their precise advantages and disadvantages, will be presented. The accessible peer-reviewed literature summarized with an important considerations on the mechanism of restraint therapy and how this acquaintance can be accustomed to optimize and improve its effectiveness.

An Immunogenic Peptide, T2 Induces Interstitial Cystitis/Painful Bladder Syndrome: an Autoimmune Mouse Model for Interstitial Cystitis/Painful Bladder Syndrome.

The exact pathophysiology of interstitial cystitis/painful bladder syndrome is unknown; however, autoimmunity is a valid theory. We developed an autoimmune chronic cystitis model by administration of the medium dose of immunogenic peptide T2. Sixty female C57BL/6 mice were divided into six groups. The control group was not treated with any reagent. CFA group was injected with CFA + normal saline, homogenate group with bladder homogenate + CFA, low-dose group with low dose of T2 peptide + CFA, medium dose group with the medium dose of T2 peptide + CFA, and high-dose group with the high dose of T2 peptide + CFA. Micturition habits, withdrawal frequencies of mice, and bladders weight were measured for each group. Hematoxylin and eosin staining and toluidine blue staining were used to investigate bladder inflammation and mast cells accumulation, respectively. T cells infiltration in the bladder tissues and serum TNF-α level were measured by using immunohistochemistry and ELISA, respectively. Mice immunized with the medium dose of T2 peptide (0.225 mg/ml) were extremely sensitive to the applied force, showed greater urine frequencies, and higher bladder weights. Histologic examination revealed severe edema and inflammation in bladder tissues of medium-dose group. Extensive infiltration of T cells in bladder tissues, elevated TNF-α, and increased mast cells accumulation were observed in medium-dose group as compared to that in other groups. EAC mice model established by injecting the medium dose of T2 (0.225 mg/ml) mimics all the symptoms and pathophysiologic characteristics of IC/PBS. We believe that this model can help us to investigate the pathogenesis of IC/PBS.

Technology Resource, Distribution, and Development Characteristics of Global Influenza Virus Vaccine: A Patent Bibliometric Analysis.

Influenza virus vaccine (IVV) is a promising research domain that is closely related to global health matters, which has been acknowledged not only by scientists and technology developers, but also by policy-makers. Meanwhile, patents encompass valuable technological information and reflect the latest technological inventions as well as the innovative capability of a nation. However, little research has examined this up-and-coming research field using patent bibliometric method. Thus, this paper (a) designs the technology classification system and search strategy for the identification of IVV; and (b) presents a longitudinal analysis of the global IVV development based on the European Patent Office (EPO) patents. Bibliometric analysis is used to rank countries, institutions, inventors and technology subfields contributing to IVV technical progress. The results show that the global trends of IVV are a multi-developing feature of variety but an uneven technical resource distribution. Although the synthetic peptide vaccine is a comparatively young field, it already demonstrates the powerful vitality and the enormous development space. With the worldwide competition increasing, all nations especially China should be looking to increase devotion, enhance capability and regard effectiveness of technological innovation.

Analyses of polycyclic aromatic hydrocarbons in seafood by capillary electrochromatography-atmospheric pressure chemical ionization/mass spectrometry.

In this work, an on-line preconcentration capillary electrochromatographic (CEC) separation coupled with atmospheric pressure chemical ionization-mass spectrometry (APCI-MS) was used for 16 PAHs analyses, in which poly(stearyl methacrylate-divinylbenzene) (poly(SMA-DVB)) monolith was used as the separation column. With variations in the effective length of poly(SMA-DVB) monolith as well as the volume fraction of acetonitrile (ACN) in the mobile phase, both separation and resolution were improved. A poly(SMA-DVB) monolith of 50-cm effective length (i.e. 50-cm column length filled with polymer) and a two-step step-gradient elution (by changing the ACN levels of the mobile phase starting with an initial of 70% up to 80% with 30-min time interval), which provided baseline separation for PAHs solutes (except for chrysene and benzo[a]anthracene) within 50 min, were employed as the optimal chromatographic conditions. In contrast to the other mass spectrometer parameters (nebulizer gas pressure, vaporizer temperature, corona current) as well as on-line preconcentration parameter (the ACN level in the sample matrix), the sheath liquid composition (methanol/water in the ratio of 3:1) and the sample injection time (40 min) were found as the predominant factors that control the sensitivity of PAHs determination. Finally, this on-line preconcentration CEC-APCI-MS method determined PAH residues in seafood samples successfully with as low as 10 ng/g level.

Metal organic framework-organic polymer monolith stationary phases for capillary electrochromatography and nano-liquid chromatography.

In this study, metal organic framework (MOF)-organic polymer monoliths prepared via a 5-min microwave-assisted polymerization of ethylene dimethacrylate (EDMA), butyl methacrylate (BMA), and 2-acrylamido-2-methylpropane sulfonic acid (AMPS) with the addition of various weight percentages (30-60%) of porous MOF (MIL-101(Cr)) were developed as stationary phases for capillary electrochromatography (CEC) and nano-liquid chromatography (nano-LC). Powder X-ray diffraction (PXRD) patterns and nitrogen adsorption/desorption isotherms of these MOF-organic polymer monoliths showed the presence of the inherent characteristic peaks and the nano-sized pores of MIL-101(Cr), which confirmed an unaltered crystalline MIL-101(Cr) skeleton after synthesis; while energy dispersive spectrometer (EDS) and micro-FT-IR spectra suggested homogenous distribution of MIL-101(Cr) in the MIL-101(Cr)-poly(BMA-EDMA) monoliths. This hybrid MOF-polymer column demonstrated high permeability, with almost 800-fold increase compared to MOF packed column, and efficient separation of various analytes (xylene, chlorotoluene, cymene, aromatic acids, polycyclic aromatic hydrocarbons and trypsin digested BSA peptides) either in CEC or nano-LC. This work demonstrated high potentials for MOF-organic polymer monolith as stationary phase in miniaturized chromatography for the first time.

Poly(triallyl isocyanurate-co-ethylene dimethacrylate-co-alkyl methacrylate) stationary phases in the chromatographic separation of hydrophilic solutes.

This study describes the ability of triallyl isocyanurate (TAIC)-co-methacrylate ester polymer monoliths as stationary phases for the separation of hydrophilic compounds (phenolic acids, amino acids and catecholamines) in capillary electrochromatography (CEC) and ultra high pressure liquid chromatography (UHPLC). Several TAIC-co-methacrylate ester polymer monoliths prepared by single-step in situ copolymerization of TAIC, ethylene dimethacrylate (EDMA) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS), with or without alkyl methacrylates were characterized by examining the SEM image, surface area, contact angle, and the thermal decomposition temperature. Compared to the conventional methacrylate ester-based monoliths, these proposed monoliths possessed hydrophilic character thus increased wettability which improved chromatographic separation selectivity of polar phenolic acids. Among the proposed TAIC-co-methacrylate monoliths, poly(TAIC-co-EDMA-AMPS-co-stearyl methacrylate (SMA)) showed separation selectivity with an increased analyte resolution from 0.0 to 0.92 for 4-hydroxybenzoic acid and vanillic acid, which were consistently difficult to resolve in the reversed-phase chromatographic mechanism of these monoliths in aqueous mobile phases. Moreover, stable ionization efficiencies were observed when this monolith was combined with ESI-MS detector possibly because an organic solvent-rich sheath liquid was used in the CEC-MS. This study demonstrates the potentiality of novel TAIC-co-methacrylate polymer monoliths in hydrophilic solute separation either in CEC or UHPLC mode.

Ionic liquids as porogens in the microwave-assisted synthesis of methacrylate monoliths for chromatographic application.

Several imidazolium-based ionic liquids (ILs) with varying cation alkyl chain length (C(4)-C(10)) and anion type (tetrafluoroborate ([BF(4)](-)), hexafluorophosphate ([PF(6)](-)) and bis(trifluoromethylsulfonyl)imide ([Tf(2)N](-))) were used as reaction media in the microwave polymerization of methacrylate-based stationary phases. Scanning electron micrographs and backpressures of poly(butyl methacrylate-ethylene dimethacrylate) (poly(BMA-EDMA)) monoliths synthesized in the presence of these ionic liquids demonstrated that porosity and permeability decreased when cation alkyl chain length and anion hydrophobicity were increased. Performance of these monoliths was assessed for their ability to separate parabens by capillary electrochromatography (CEC). Intra-batch precision (n=3 columns) for retention time and peak area ranged was 0.80-1.13% and 3.71-4.58%, respectively. In addition, a good repeatability of RSD(Retention time)=<0.30% and ~1.0%, RSD(Peak area)=<1.30% and <4.3%, and RSD(Efficiency)=<0.6% and <11.5% for intra-day and inter-day, respectively exemplify monolith performance reliability for poly(BMA-EDMA) fabricated using 1-hexyl-3-methylimidazolium tetrafluoroborate ([C(6)mim][BF(4)]) porogen. This monolith was also tested for its potential in nanoLC to separate protein digests in gradient mode. ILs as porogens also fabricated different alkyl methacrylate (AMA) (C4-C18) monoliths. Furthermore, employing binary IL porogen mixture such as 1-butyl-3-methylimidazolium tetrafluoroborate ([C(4)mim][BF(4)]) and 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C(4)mim][Tf(2)N]) successfully decreased the denseness of the monolith, than when using [C(4)mim][Tf(2)N] IL alone, enabling a chromatographic run to be performed with 1:1 ratio produced baseline separation for the analytes. The combination of ILs and microwave irradiation made polymer synthesis very fast (~10min), entirely green (organic solvent-free) and energy saving process.

Capillary electrochromatography-mass spectrometry determination of melamine and related triazine by-products using poly(divinyl benzene-alkene-vinylbenzyl trimethylammonium chloride) monolithic stationary phases.

In this study, a capillary electrochromatography (CEC) method coupled either with UV or mass spectrometric detection was developed for the detection of trace-amounts of melamine and its related by-products (ammeline, ammelide, and cyanuric acid). A series of poly(divinyl benzene-alkene-vinylbenzyl trimethylammonium chloride) monolithic columns, which were prepared by a simple in situ polymerization with divinyl benzene (DVB), vinylbenzyl trimethylammonium chloride (VBTA) and different types of alkene monomers such as 1-octene, 1-dodecene or 1-octadecene were used as separation columns, with the poly(DVB-1-dodecene-VBTA) monolith as the optimal chromatographic material because it provided a better separation. The detection limits of four melamine derivatives were in the ranged of 0.6-2.18 mg L(-1) by the optimal CEC-UV mode, and were reduced from 2.2 to 19.4 µg L(-1) by the optimal CEC-MS mode. Finally, the proposed CEC methods successfully determined melamine contaminations (0.1 mg L(-1) per analyte) in several dairy products as test samples with analyte recovery range of 69-85% (intra-day) and 68-75% (inter-day), and with peak area reproducibility range of 4.3-8.6% and 8.7-15.6% for intra-day and inter-day, respectively. This is the first report for CEC separation coupled with MS detection applied in trace melamine residue analyses with a faster separation and comparable or even better detection ability than previous GC-MS, CE-MS, as well as LC-MS methods.

Analyses of sulfonamide antibiotics in meat samples by on-line concentration capillary electrochromatography-mass spectrometry.

In this work, a series of poly(divinylbenzene-alkyl methacrylate) monolithic stationary phases, which were prepared by single step in situ polymerization of divinylbenzene and various alkyl methacrylates (butyl-, octyl-, lauryl- or stearyl methacrylate), were developed as separation columns of nine common sulfonamide antibiotics for capillary electrochromatography (CEC) coupled to mass spectrometry (MS). Results indicated that the sulfonamide's retention became weak with increased carbon chain length of alkyl methacrylate monomer (for example, t(R)=68 min and 21 min for butyl- and lauryl methacrylate, respectively). Among them, the poly(divinylbenzene-octyl methacrylate) (poly(DVB-OMA)) monolith was regarded as the optimal separation column as this provided better resolution within the shortest retention time. Moreover, the cross-sectional roughness of the monolithic column-end, that was used to couple to the ESI interface, strongly influenced the electrospray stability in the CEC-MS. Before the column was connected to the ESI-MS, a simple polishing was done to reduce the roughness of the column end that resulted to a great improvement in the signal stability. The relative standard deviations (RSDs) of the peak areas for the unpolished and polished ends of the poly(DVB-OMA) columns (n=5) were in the range of 46.1-60.2% and 8.9-16.4%, respectively. Furthermore, optimization of the mobile phase composition and the gradient elution strategy successfully determined the sulfonamide antibiotics in meat samples with as low as 10 µg/L level.

Analyses of non-steroidal anti-inflammatory drugs by on-line concentration capillary electrochromatography using poly(stearyl methacrylate-divinylbenzene) monolithic columns.

This study describes the ability of on-line concentration capillary electrochromatography (CEC) coupled with UV or mass spectrometry (MS) for the determination of nine common non-steroidal anti-inflammatory drugs (NSAIDs) in water samples. A series of poly(stearyl methacrylate-divinylbenzene) (poly(SMA-DVB)) monolithic columns, which were prepared by single step in situ polymerization of divinylbenzene (DVB), stearyl methacrylate (SMA) and vinylbenzenesulfonic acid (VBSA, charged monomer), were developed as separation columns for the first time. The effects of polymerization condition of monolithic columns on analyte separations were examined, and the results indicated that separation performances were markedly improved in monolithic columns prepared with short reaction time (3 h) and low SMA:DVB ratio (40/60 ratio of SMA:DVB). Subsequently, an on-line concentration step of step-gradient elution was combined to this CEC system, and by optimizing the difference in eluent strength between the sample matrix and mobile phase, all NSAIDs detection sensitivity were improved (limit of detection (LOD) was 3.4-10 µg/L for UV, and 0.01-0.19 µg/L for MS). When compared to the best CE and LC reports on NSAIDs analyses so far, this on-line concentration CEC method provided better detection ability within shorter separation time (12 min) when either UV or MS detector was employed. This is the first report for on-line concentration CEC with MS detection applied in trace solute analyses of real samples.