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BACKGROUND: The topical veterinary drug product containing fipronil and permethrin provides an effective repellent protection and high insecticidal efficacy for dogs. OBJECTIVE: The objective of this study was to develop a stability-indicating high-performance liquid chromatography (HPLC) method for simultaneous detection and quantification of fipronil, permethrin, their key degradation products, and butylated hydroxytoluene (BHT) in a topical drug product. METHOD: The two active ingredients, their degradation products, and the antioxidant (BHT) were separated by a gradient elution on a Phenomenex Kinetex C18 column (150 × 3 mm, 2.6 µm particle size) maintained at 37°C with H2O acetonitrile isopropyl alcohol 85% H3PO4 (65.5 + 32.5 + 4/0.0053, v/v/v/v) as mobile phase A and acetonitrile (100%) as mobile phase B. The flow rate was 0.9 mL/min, and analytes were detected and quantified at 235 nm. RESULTS: The specificity of the method was demonstrated by adequate separation of fipronil, permethrin, their degradation products, and BHT in the forced degraded finished product. The linearity of the method was demonstrated in the range of 0.2% to 150% of target analytical concentration of both active ingredients and 50% to 150% for BHT. Excellent recoveries of fipronil, permethrin, and BHT in placebo spiked active ingredient solutions in the linearity range showed sufficient accuracy of the method. The LOQ and LOD of the method were determined to be 0.2% and 0.07% of the analytical concentration. A robustness study did not identify any critical parameter that adversely affected the separation and quantification. CONCLUSIONS: Here, we report the development and validation of a robust, stability-indicating HPLC method for identification and assay of fipronil, permethrin, and BHT, including estimation of fipronil's and permethrin's degradation products in a topical drug product for dogs. HIGHLIGHTS: The new HPLC method permits the acquisition of data for all analytes of interest for a topical finished drug product containing fipronil, permethrin, and BHT.
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Permetrina , Pirazoles , Permetrina/análisis , Permetrina/química , Cromatografía Líquida de Alta Presión/métodos , Pirazoles/análisis , Pirazoles/química , Insecticidas/análisis , Estabilidad de Medicamentos , Drogas Veterinarias/análisis , Administración Tópica , Límite de Detección , AnimalesRESUMEN
BACKGROUND: Single-site robotic-assisted radical prostatectomy (ssRARP) has been promoted in many institutions due to its minimally invasive approach. This review aimed to investigate early outcomes of ssRARP in comparison with multi-port robotic-assisted radical prostatectomy (mpRARP). METHODS: A systematic literature search was performed for articles related to ssRARP case series and studies that compared ssRARP with mpRARP. The primary outcomes were functional and oncological outcomes, incision length, length of hospital stay and cost. RESULTS: 24 ssRARP case series involving 1385 cases, and 11 comparative studies involving 573 ssRARP cases and 980 mpRARP cases were included. Rate of immediate, 3-month, 6-month and 12-month recovery of continence in the ssRARP case series were 41 % [95 % CI: 0.38-0.45], 70 % [95 % CI: 0.67-0.73], 90 % [95 % CI: 0.87-0.93] and 93 % [95 % CI: 0.90-0.96]. 3-month potency recovery and positive surgical margin rate were 53 % [95 % CI: 0.46-0.60] and 21 % [95 % CI: 0.19-0.24]. No significant differences were detected between ssRARP and mpRARP in terms of 3-month (OR: 1.12; 95 % CI: 0.80-1.57) or 6-month (OR: 0.72; 95 % CI: 0.36-1.46) continence recovery rate, 3-month potency recovery rate (OR: 0.92; 95 % CI: 0.50-1.70), positive surgical margin rate (OR: 0.83; 95 % CI: 0.62-1.11), biochemical recurrence rate or total cost. Furthermore, ssRARP was associated with a significantly shorter length of incision and hospital stay. CONCLUSION: ssRARP has significant advantages in cosmetic effect, length of incision and rapid recovery. Consequently, ssRARP is expected to become the preferred form although more evidence is needed to determine its long-term effect.
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Laparoscopía , Procedimientos Quirúrgicos Robotizados , Masculino , Humanos , Márgenes de Escisión , Próstata , Prostatectomía , Resultado del TratamientoRESUMEN
Photocatalytic degradation of pollutants is considered a promising approach for wastewater treatment, but is hampered by low efficiency and limited understanding of degradation pathways. A novel oxygen-doped porous g-C3N4/oxygen vacancies-rich BiOCl (OCN/OVBOC) heterostructure was prepared for photocatalytic degradation of bisphenol A (BPA). The synergistic defect and doping engineering favor the formation of strong bonded interface for S-scheme mechanism. Among them, 0.3 OCN/OVBOC showed the most excellent degradation rate, which was 8 times and 4 times higher than that of pure g-C3N4 and BiOCl, respectively. This excellent performance is mainly attributed to the significantly enhanced charge separation via strong bonded interface and redox capability of the S-scheme heterojunction structure, by tuning the coordination excitation and electron localization of the catalyst via O doping and vacancies. This work provides important insights into the role of synergistic defect and doping engineering in facilitating the formation of strong bonded S-scheme heterojunction and ultimately sheds new light on the design of efficient photocatalysts.
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Electrones , Contaminantes Ambientales , Oxígeno , PorosidadRESUMEN
Firocoxib is widely used in veterinary medicine as a non-steroidal analgesic and anti-inflammatory drug substance. Herein, a comprehensive study on the degradation profile of firocoxib was performed through force degradation studies to understand its degradation profile and characterize its major degradation products (DPs). Firocoxib drug substance was subjected to acidic, alkaline, oxidation (H2O2, KMnO4, and K2Cr2O7), thermal (solid and solution state), and photolytic (solid and solution state) stress degradation, as recommended in the ICH guidelines. Firocoxib and its major DPs were adequately separated by investigational HPLC method, which utilized a HALO C18 (100 × 2.1 mm, 2.0 µm) column. Mobile phase-A for the HPLC method is composed of 0.1% formic acid in water and mobile phase-B acetonitrile. A total of six major DPs were observed for firocoxib drug substance under these stress degradation conditions. Structural elucidation of the DPs performed using liquid chromatography-high resolution mass spectrometry and comparison of their fragmentation profile with that of the parent compound. For further structural confirmation of two major DPs, DP-2 and DP-6 were isolated and purified from the stressed samples using a preparative HPLC and analyzed by comprehensive nuclear magnetic resonance (NMR) spectroscopy studies. Most probable mechanistic pathways for the formation of DPs of firocoxib under various stress degradation conditions were postulated to understand its degradation profile. Based on the results from forced degradation, firocoxib was found to be quite stable under basic and thermal conditions, and somewhat unstable under acidic, oxidative, and photolytic conditions. The results of this study should facilitate quality monitoring and establish a stability profile of firocoxib drug substance and drug products. These results may also assist in the design and development of new formulations made with firocoxib drug substance with desired shelf life.
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Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en Tándem , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodos , Peróxido de Hidrógeno , Cromatografía Liquida/métodos , Cromatografía Líquida de Alta Presión/métodos , Estabilidad de Medicamentos , Oxidación-Reducción , Hidrólisis , FotólisisRESUMEN
Ivermectin is a potent semi-synthetic antiparasitic drug used in veterinary medicine. A reversed-phase high performance liquid chromatography (HPLC) method has been developed and validated for the identification and assay of Ivermectin, including the identification and estimation of its related impurities in an oral paste. Analytes were separated using a gradient elution at a flow rate of 1.5 mL/min on a Zorbax Extend-C18 column (150 mm × 4.6 mm i.d., 3.5-µm particle size) maintained at 30 °C. The mobile phase was composed of water as mobile-phase A and acetonitrile/methanol (85/15, v/v) as mobile-phase B. Ultraviolet detection at 245 nm was employed to monitor the analytes. Limit of quantitation (LOQ) and limit of detection (LOD) of the method are 0.6 and 0.2 µg/mL, respectively. The validation results demonstrated excellent linearity of the method in the range of 0.1-150% of the analytical concentration (0.6 mg/mL) of the method. The stability-indicating capability of the method has been demonstrated by adequately separating the degradation products from the stress degraded samples of the oral paste as per method validation requirements prescribed in the current International Council for Harmonisation guidelines.
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Bioensayo , Ivermectina , Cromatografía Líquida de Alta Presión , Proyectos de Investigación , Cromatografía de Fase InversaRESUMEN
In this work, a photoelectrochemical (PEC) aptasensor for detecting kanamycin (KAN) was designed based on an aptamer modified Bi/BiOBr/titania nanorod array (TiO2 NRA). Bi/BiOBr was loaded onto the TiO2 NRA via a one-pot solvothermal method using glucose as a reductant. The p-n heterojunction structure constructed from chrysanthemums like BiOBr and the TiO2 NRA improves the electron transfer rate. Combined with metal Bi with the surface plasmon resonance (SPR) effect, it further increases the absorption range of visible light and enhances the light response performance of the PEC aptasensor. The KAN aptamer is fixed to the Bi/BiOBr/TiO2 NRA photoelectric material through the CîN structure. Once the aptamer precisely captures KAN molecules, photocurrent changes are generated to realize the detection of KAN. The designed PEC aptasensor shows good detection performance in the linear response range of 1 pM-200 nM, and the detection limit is 0.7 pM (S/N = 3). The aptasensor was applied to the determination of KAN in milk with satisfactory results.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Nanotubos , Aptámeros de Nucleótidos/química , Bismuto , Técnicas Electroquímicas/métodos , Kanamicina , Límite de Detección , Nanotubos/química , TitanioRESUMEN
Antibiotic contamination has received widespread attention globally. In this work, the oxygen-doped porous graphite carbonitride (g-C3N4) was prepared with urea and ammonium oxalate (CNUC) or urea and glycine (CNUG) as precursors by thermal polymerization. Using bisphenol A (BPA) as a probe and CNUC or CNUG as photocatalysts, the removal performance test was carried out. Meanwhile, all prepared photocatalysts were characterized by XRD, FT-IR, SEM, TEM, XPS, UV-Vis DRS, PL and EIS. Under visible light irradiation, both CNUC and CNUG exhibited about seven and five times greater photocatalytic activity than that of pure g-C3N4, respectively. The radical capture experiments verified that superoxide radicals (â¢O2-) and holes (h+) were the main active species in the photocatalytic degradation of BPA by CNUC, and the possible photocatalytic mechanism of CNUC was proposed. In addition, all these results indicate that CNUC catalyst can effectually inhibit the photocorrosion and keep superior stability. The proposed technique provides a prospective approach to develop nonmetal-modified photocatalysts for future applications.
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Developing a photoactive material by combining the characteristics of a wide light response range and effective separation of photogenerated electron-hole pairs remains a huge challenge for the construction of a photoelectrochemical (PEC) sensing platform. Herein, a gold nanoparticle (AuNP)/MoS2/TiO2 composite was prepared through the facile hydrothermal method coupled with an in situ photoreduction technology. Benefiting from both the compositional and structure merits, the composite not only extends the absorption range to visible light but also enhances the photoelectric conversion efficiency by transferring photogenerated electrons into the conduction band of semiconductors from the plasmonic AuNP. Meanwhile, the thiolated aptamers were attached to the surface of AuNP/MoS2/TiO2 composites through the Au-S bonding to construct a visible light driven PEC aptasensor for ultrasensitive detection chloramphenicol (CAP). In the presence of CAP, the aptamers anchored on the surface of the photoactive materials could specifically recognize CAP and interact with it to form a bioaffinity complex with a steric hindrance effect, resulting in the rapid decrease of photocurrent responses. Based on this photocurrent suppression strategy, the constructed PEC aptasensing platform exhibited a high sensitivity with a wide linear range from 5 pM to 100 nM and a low detection limit of 0.5 pM.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Nanopartículas del Metal , Aptámeros de Nucleótidos/química , Cloranfenicol , Técnicas Electroquímicas/métodos , Oro/química , Luz , Límite de Detección , Nanopartículas del Metal/química , Molibdeno/química , TitanioRESUMEN
Cobalt doped Bi25FeO40 was used as a heterogeneous catalyst in microwave (MW) co-activation of peroxydisulfate (PDS) system for organic contaminant purification and disinfection simultaneously. Due to low charge-transfer resistance and fast electron migration, Co-Bi25FeO40 showed superior catalytic efficiencies for activation PDS to degrade over 92.0% of bisphenol A (BPA) with the initial concentrations ranging from 40 mg/L to 120 mg/L in 5.0 min. The non-radical oxidation pathway via electron transfer regime on the surface of Co-Bi25FeO40 was the dominant reactive species in the reaction system. Benefit from the energy transfer and cross-coupling reactions of microwave, the Co-Bi25FeO40/MW/PDS system can generate abundant reactive sites to facilitate the formation of more surface-bonding complexes. Microwave energy can be absorbed by Co-Bi25FeO40 catalysts to promote activation of PDS and production of nanobubbles. The generated nanobubbles increase the temperature of the local solution to promote the reaction. The Co-Bi25FeO40/MW/PDS system also exhibited excellent bactericidal capability for Escherichia coli (E.coli). The catalysts, oxidants and microwaves acted on E. coli to form physical, and oxidative pressure simultaneously, causing cell damaged and made bacterial death. This work provides prospects toward high-efficiency integration of contaminant purification and pathogenic microorganisms inactivation.
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Desinfección , Contaminantes Ambientales , Electrones , Escherichia coli , MicroondasRESUMEN
Objective: To assess the feasibility and validity of the establishment of a modified channel for extraperitoneal robot-assisted laparoscopic radical prostatectomy (RARP) through single incision. METHODS: From November 2020 to January 2021, 35 cases of localized PCa were treated by extraperitoneal RARP through single incision in our center. All the operations were performed by the same surgeon, none via the multichannel port for the establishment of the channel. We recorded and analyzed the intra- and postoperative parameters, operation cost, complications, pathological findings and follow-up data. RESULTS: All the operations were successfully completed, without conversion to open surgery or additional channels, or serious postoperative complications, the time for establishing the extraperitoneal space averaging 25.4 (20.0ï¼45.0) min, the operation time 67.3 (35.0ï¼125.0) min, intraoperative blood loss 75.5 (60.0ï¼150.0) ml, time to first postoperative anal exhaust 26 (8ï¼48) h, and postoperative hospital stay 7.89 (7ï¼10) d. Postoperative pathology showed adenocarcinoma in all the cases, with Gleason score (GS) 3+3 in 9 (25.7%), GS 3+4 in 9 (25.7%), GS 4+3 in 8 (22.9%), and GS ≥ 8 in 9 (25.7%) of the cases, 23 (65.7%) in the Asunto(s)
Laparoscopía
, Procedimientos Quirúrgicos Robotizados
, Robótica
, Pérdida de Sangre Quirúrgica
, Humanos
, Masculino
, Prostatectomía
RESUMEN
A micro-channel distillation device was used for the process intensification method to separate boron isotopes, 10B and 11B. Three-dimensional (3D) printing technology was introduced to manufacture the micro-channel device, which used the chemical exchange method with anisole as the donor to separate the boron isotopes. This device was tested in total reflux mode, and the height of an equivalent theoretical plate of the micro-channel distillation equipment was reduced to 1.56 cm. The accurate control of pressure and temperature, as well as the flow rate of the complex, were factors that affected separation ability. Thus, for process intensification, this micro-channel distillation device can be operated horizontally and connected in series into similar modules to effectively improve separation efficiency and reduce the size of the equipment.
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BACKGROUND: Eprinomectin is used as an active pharmaceutical ingredient (API) in various drug products by the animal health industry. Several major related impurities of eprinomectin API are not separated and coelute by the current United States Pharmacopeia (USP) method for eprinomectin. OBJECTIVE: The aim was to develop and validate a true and reliable stability-indicating reversed-phase (RP) HPLC method for assay and determination of related substances of eprinomectin in bulk batches of eprinomectin API. METHOD: HPLC analysis is carried out using a Kinetex C8 column (100 mm × 4.6 mm i.d. , 2.6 µm particle size) maintained at 30°C with water-acetonitrile-isopropanol (48 + 42 + 10, v/v/v) as mobile phase A and 100% acetonitrile as mobile phase B. Analytes are separated by gradient elution at a flow rate of 0.7 mL/min and detected by UV at 252 nm. The total run time of the method is 30 min. Eprinomectin assay and estimation of all eprinomectin-related substances are obtained in a single HPLC run. RESULTS: The HPLC method was able to separate all analytes of interest by gradient elution. The new method was successfully validated according to current The Internal Council for Hamonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and International Cooperation on Hamonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) guidelines and was found to be specific, linear, accurate, precise, robust, and sensitive. CONCLUSIONS: An HPLC method for assay of eprinomectin and estimation of its related substances was successfully developed, validated, and demonstrated to be accurate, robust, specific, and stability-indicating. HIGHLIGHTS: The HPLC method presented in this paper is more desirable as compared to USP and suitable for routine analysis of bulk batches of eprinomectin API and stability samples in QC laboratories.
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Ivermectina , Preparaciones Farmacéuticas , Bioensayo , Cromatografía Líquida de Alta Presión , Estabilidad de Medicamentos , Humanos , Ivermectina/análogos & derivadosRESUMEN
TiO2/porous glass-H as composite catalysts were synthesized hydrothermally in the presence of H2O2 using porous glass microspheres as carriers. The photocatalytic-adsorptive desulfurization of model fuel by composite catalysts was investigated under UV irradiation. The structure and morphology of the composite catalysts were characterized via scanning electron microscopy (SEM), N2 adsorption, X-ray diffraction (XRD) and ultraviolet-visible spectroscopy (UV-vis). The results showed that TiO2/porous glass-H exhibited a significantly enhanced photocatalytic-adsorption desulfurization performance due to its enhanced surface area, highly enhanced light absorption, and reduced recombination of photogenerated electron pairs compared with TiO2/porous glass synthesized in the absence of H2O2. The optimized TiO2 loading was 20% and the reaction temperature was 303.15 K, which could achieve almost 100% sulfur removal when 0.1 g catalyst was applied to a sulfide concentration of 300 mg L-1. Based on the kinetic fitting of the obtained data, it was found that the rate-controlling step of sulfide adsorption on the catalyst was a molecular diffusion process and the adsorption intensity and adsorption capacity of the composite catalyst were significantly improved compared with the porous glass-H in the adsorption thermodynamic curve, and ΔS, ΔH and ΔG of the adsorption process were calculated. In addition, TiO2/porous glass-H could be regenerated via simple heat treatment, exhibiting similar efficiency as the original TiO2/porous glass-H after three regeneration cycles.
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BACKGROUND: Cavernous hemangioma, as a rare tumor, is difficult to differentiate from retroperitoneal lymphoma and paraganglioma. They are more difficult to excise completely through open surgery and traditional laparoscopic surgery. The study aimed to evaluate the role of DaVinci surgical system in laparoscopic resection of parapelvic cavernous hemangioma. CASE PRESENTATION: A 46-year-old female, who diagnosed as parapelvic cavernous hemangioma accompanying with thrombosis and calcification, was performed laparoscopic resection using DaVinci surgical system under general anesthesia. The patient well recovered without recurrence or spread of the lesion after operation for 3 months as well as hydronephrosis was significantly relieved. CONCLUSION: Laparoscopic resection of parapelvic cavernous hemangioma under the help of DaVinci surgical system was feasible and safe.
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Hemangioma Cavernoso , Laparoscopía , Neoplasias Pélvicas , Neoplasias Retroperitoneales , Procedimientos Quirúrgicos Robotizados , Femenino , Hemangioma Cavernoso/diagnóstico por imagen , Hemangioma Cavernoso/cirugía , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Pélvicas/diagnóstico por imagen , Neoplasias Pélvicas/cirugía , Neoplasias Retroperitoneales/diagnóstico por imagen , Neoplasias Retroperitoneales/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Magnetic graphene nanocomposites were prepared by hydrothermal synthesis, and aniline polymerization was initiated by magnetic graphene. These polyaniline/magnetic graphene (PANI/MG) composites were used to immobilize laccase to construct biosensors. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and infrared spectroscopy (IR) were used to characterize these composites. Cyclic voltammetry and chronoamperometry technique were used to test the electrical properties of the constructed polyaniline/magnetic graphene laccase modified electrode. The results show that the polyaniline/magnetic graphene immobilizing laccase modified electrode exhibited superior electrical properties, including high sensitivity, detection limit and linear range. The hydroquinone was used as an analytical and detection probe. The selectivity was 0.03639 A/(mol/L), the linear range was 0.4-337.2 µmol/L, and the detection limit was 2.94 µM (signal/noise = 3, minimum identification value of effective signal). The biosensor can reach the conditions for detecting the actual water sample.
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Compuestos de Anilina/química , Enzimas Inmovilizadas/metabolismo , Grafito/química , Hidroquinonas/análisis , Lacasa/metabolismo , Fenómenos Magnéticos , Técnicas Biosensibles , Carbono/química , Catálisis , Electroquímica , Electrodos , Vidrio/química , Espectroscopía Infrarroja por Transformada de Fourier , Agua/químicaRESUMEN
In this work, polylactic acid/thermoplastic acetylated starch (PLA/TPAS) composites were prepared using PLA as a matrix material and TPAS as a modifier. TPAS is based on acetylated starch, which is plasticized using glycerin. Analysis of the mechanical, thermal, and dynamic mechanical properties, and morphological structures of the PLA/TPAS composites shows that with an increase in the TPAS content, the toughness of the PLA/TPAS composites significantly improves. When the amount of TPAS added is 40% by weight, the elongation at break is increased 4 times. At the same time, the addition of TPAS has little effect on the thermal stability of the composites. Differential scanning calorimetry (DSC), dynamic mechanical analysis and scanning electron microscopy (SEM) analysis results show that PLA is incompatible with TPAS. The addition of TPAS promotes the crystallization of PLA, resulting in a decrease in the thermal stability but limits the degradation behavior during the processing of the material, which has little effect on the performance of the material. High temperature and high humidity soil degradation and ultraviolet radiation aging experiments on PLA/TPAS composites show that the PLA/TPAS composites have good biodegradability. In soil burial degradation experiments, the degradation rate of the pure PLA material is slow, and its final mass retention rate is high. The PLA/TPAS composites degrade fast. In ultraviolet radiation aging experiments, the tensile strength of the PLA/TPAS composites was improved to a certain extent after exposure to ultraviolet radiation. With an increase in the ultraviolet irradiation time, the tensile properties of the PLA/TPAS composites gradually decreased.
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Effective separation and rapid transfer of photogenerated electron-hole pairs are key features of photocatalytic materials with high catalytic activity, which could be achieved in co-catalysts. It is reported that the two-dimensional (2D) MoS2 is a promising co-catalyst due to its unique semi-conductive properties and graphene-like layered structure. However, the application of MoS2 as a co-catalyst is limited by its poor electrical conductivity. On the other hand, it is worth noting that TiO2 possesses reactive crystal facets, which is one of the dominant mechanisms for the separation of photogenerated electron-hole pairs. In this work, we prepared MoS2/RGO hybrids as co-catalysts which were doped to TiO2 with highly reactive {001} planes via the hydrothermal method. It was found that the {001}-TiO2/MoS2/RGO photocatalysts with 7 wt% MoS2/RGO co-catalyst show the highest photodegradation activity for the degradation of Rh B under visible light irradiation (λ > 400 nm), which could result from the synergy of the effective separation of electron-hole pairs by the {001} facets in TiO2 and the rapid transfer of electron-hole pairs in MoS2/RGO. The results show that the {001}-TiO2/MoS2/RGO hybrid is a low-cost and stable photocatalyst for the effective degradation of Rh B under visible light.
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Imidacloprid is used as an active pharmaceutical ingredient (API) in veterinary drugs to control fleas and ticks for dogs and cats. Here we are reporting for the first time a validated stability-indicating reversed-phase UPLC-UV method for the assay of imidacloprid and estimation of its related compounds. The stability-indicating capability of this method has been demonstrated by a forced degradation study. All related compounds including processing impurities, imidacloprid API and degradates from stressed samples were well separated from each other. Structures of major degradates from forced degradation study were elucidated through UPLC-MS/MS and key degradation pathways were proposed from the proposed chemical structures of major degradates. The UPLC-UV method is carried out using an HSS T3 column (C18, 2.1 × 30 mm, 1.8 µm particle size) maintained at 30°C with mobile phase A (0.05% v/v of phosphoric acid in water) and mobile phase B (methanol/acetonitrile 75/25 v/v). Analytes are separated by a gradient elution and detected at 270 nm. The UPLC method is green and fast with only 6.5 min run time and about 3.5 ml mobile phase consumption for each sample analysis. The UPLC-UV method was validated according to ICH guidelines.