Novel VEGFR2 inhibitors with thiazoloquinoxaline scaffold targeting hepatocellular carcinoma with lower cardiotoxic impact.

Hepatocellular carcinoma (HCC) is a fatal tumor which is usually diagnosed at advanced stage. Molecular targeted drugs were used recently to treat HCC, however, due to serious side effects, mainly cardiotoxicity and emergence of resistance, there is demanding to explore new chemotherapeutics. 10 novel thiazoloquinoxaline derivatives coupled with different sulfonamide moieties 4(a-j) were designed and synthesized fulfilling pharmacophoric features of VEGFR-2 inhibition. Structures of all new compounds were verified via spectral and microanalytical data. After carrying in-vitro VEGFR-2 assay for compounds 4(a-j); sulfapyridine and sulfamethoxazole derivatives 4d and 4f showed potential inhibitory effect [61.04 and 83.35 nM], respectively, comparable to standard sorafenib [51.41 nM]. Both were then further evaluated for their cytocidal activity against HepG2 cell-line and against myocardium cells using H9C2 cell-line. As a result, only sulfapyridine derivative 4d exhibited a significant inhibition of HepG2 cells viability [IC50 = 4.31 µM]. Furthermore, it showed relatively lower cytotoxic impact against normal H9C2 myocardium cells [IC50, 33.47 µM] compared to that of sorafenib [IC50, 98.07 µM]. In-vivo study was carried out to determine myocardium safety of compound 4d on irradiated mice (8 Gy). In-vivo results of sulfapyridine derivative 4d showed normal cardiac enzyme function (CK) and serum catalase activity with significant reductions in LDH, cardiac TNF-α and caspase-9 levels, alongside with its efficacy in suppressing the expression of hepatic VEGF. In conclusion, sulfapyridine derivative 4d could be considered a promising candidate as VEGFR-2 inhibitor with less myocardium side effect.

An LC-MS/MS method for the simultaneous quantitation of sulfasalazine and sulfapyridine in human placenta.

Sulfasalazine has been identified as a candidate molecule to be investigated as an intervention to treat preterm pre-eclampsia during pregnancy. However, placental exposure of sulfasalazine and its systemically absorbed metabolite, sulfapyridine, is unknown. A robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously quantitate these analytes in human placenta with an application to a pilot clinical trial. The placental tissue was homogenised using a water:methanol (1:1, v/v) mixture, followed by sample extraction using both protein precipitation and solid phase extraction. Sulfasalazine-d4 and sulfapyridine-d4 were used as internal standards. An Agilent Poroshell EC-C18 (3.0 ×100 mm, 2.7 µm) column was used for chromatographic separation, with gradient elution employed at a flow rate of 0.450 mL/min over a total run time of seven minutes. The mobile phases consisted of water with 0.1% formic acid (mobile phase A) and acetonitrile:methanol (90:10, v/v) with 0.1% formic acid (mobile phase B). A Shimadzu-8040 mass spectrometer was operated in multiple reaction monitoring (MRM) mode using positive electrospray ionisation (ESI). For both analytes, the assay was validated over the range 30-30,000 ng/mL, or 150-150,000 ng/g. During inter-day validations (n = 18), the average accuracies of quality controls ranged from 101.6% to 112.7% with corresponding precisions of 4.4-6.7% for sulfasalazine, and from 97.4% to 108.4%, with corresponding precisions of 3.7-10.0% for sulfapyridine. No significant matrix effects were observed, and the method proved to be sensitive and specific for both analytes. This study presents the first validated analytical method for quantifying sulfasalazine and sulfapyridine in human placenta as part of a pilot clinical trial to generate preliminary data on its pharmacokinetics and efficacy as in intervention for preterm pre-eclampsia.

[Pollution Characteristics and Risk Assessment of Antibiotics in Beiyun River Basin in Beijing].

To investigate the pollution characteristics and risk levels of antibiotics in water of the Beiyun River Basin in Beijing, the concentration of antibiotics was analyzed by using the solid-phase extraction and high-performance liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) method. The results showed that seven types of four categories of antibiotics were detected in the samples from 12 sampling points; the total concentration of antibiotics including sulfapyridine, clarithromycin, azithromycin, roxithromycin, erythromycin, ofloxacin, and lincomycin ranged from 59.19 to 703.44 ng·L-1. Among these antibiotics, the detection rate of clarithromycin, azithromycin, roxithromycin, ofloxacin, and lincomycin was 100%; that of erythromycin was 41.67%; and that of sulfapyridine was 33.33%. Compared with that in some rivers in China, the Azithromycin, Erythromycin, and Clarithromycin in the Beiyun River Basin were at a relatively high level. The ecological risk assessment results showed that the most sensitive species was algae. The health risk quotients indicated that sulfapyridine, lincomycin, roxithromycin, azithromycin, and erythromycin presented no risk for every age group, whereas the health risk of clarithromycin was at a low level.

Single-step electropolymerization on a printed sensor towards a conductive thin film polymer for the simultaneous determination of drug metabolites: 5-aminosalicylic acid and sulfapyridine.

Amino acid conductive polymers can easily form a thin film on a sensor surface by an electrochemical process. Therefore, we are pioneers in reporting the electropolymerization of L-methionine on the surface of a screen-printed graphene electrode to obtain a disposable electrochemical sensor for determining drug metabolites (5-aminosalicylic acid (5-ASA) and sulfapyridine (SPD)) of sulfasalazine (SSZ) simultaneously. In this work, the developed sensor was facilely created through a single step of electropolymerization under mild conditions (0.1 M phosphate buffer pH 7.0) using cyclic voltammetry. Important parameters in the synthesis process were systematically investigated followed by surface composition and morphology studies. Then, analytical performances, comprising sensitivity, selectivity, stability, reproducibility, and sample preparation, were carefully evaluated. Under optimal conditions, the proposed methodology demonstrated a highly sensitive and selective simultaneous detection of 5-ASA and SPD with wide linear dynamic ranges of 1-50 µM and 80-250 µM and low detection limits of 0.60 and 0.57 µM for 5-ASA and SPD, respectively. To evaluate the potential of the designed sensor, it was successfully applied by simultaneously determining 5-ASA and SPD in real human urine samples on the same day (intra-day study) and on three different days (inter-day study).

Indirect photodegradation of sulfadimidine and sulfapyridine: Influence of CDOM components and main seawater factors.

This study investigated the indirect photodegradation of sulfadimidine (SM2) and sulfapyridine (SP) in the presence of chromophoric dissolved organic matter (CDOM), and studied the influences of main marine factors (salinity, pH, NO3- and HCO3-). Reactive intermediate (RI) trapping experiments demonstrated that triplet CDOM (3CDOM*) played a major role in the photodegradation of SM2 with a 58% photolysis contribution, and the contributions to the photolysis of SP were 32%, 34% and 34% for 3CDOM*, hydroxyl radical (HO·) and singlet oxygen (1O2), respectively. Among the four CDOMs, JKHA, with the highest fluorescence efficiency, exhibited the fastest rate of SM2 and SP photolysis. The CDOMs were composed of one autochthonous humus (C1) and two allochthonous humus (C2 and C3). C3, with the strongest fluorescence intensity, had the strongest capacity to generate RIs and accounted for approximately 22%, 11%, 9% and 38% of the total fluorescence intensity of SRHA, SRFA, SRNOM and JKHA, respectively, indicating the predominance of CDOM fluorescent components in the indirect photodegradation of SM2 and SP. These results demonstrated the photolysis mechanism: The photosensitization of CDOM occurred after its fluorescence intensity decreased, and a large number of RIs (3CDOM*, HO· and 1O2, etc.) were generated by energy and electron transfer, then these RIs reacted with SM2 and SP to cause photolysis. The increase in salinity stimulated the photolysis of SM2 and SP consecutively. The photodegradation rate of SM2 first increased and then decreased with increasing pH, whereas the photolysis of SP was remarkably promoted by high pH but remained stable at low pH. NO3- and HCO3- had little effect on the indirect photodegradation of SM2 and SP. This research may contribute to a better understanding of the fate of SM2 and SP in the ocean and provide new insights into the transformation of other sulfonamides (SAs) in marine ecological environments.

Fixed bed column experiments using cotton gin waste and walnut shells-derived biochar as low-cost solutions to removing pharmaceuticals from aqueous solutions.

Acetaminophen (ACT), sulfapyridine (SPY), ibuprofen (IBP) and docusate (DCT) are pharmaceuticals with widespread usage that experience incomplete removal in wastewater treatment systems. While further removal of these pharmaceuticals from wastewater effluent is desired prior to beneficial reuse, additional treatment technologies are often expensive and energy intensive. This study evaluated the ability of biochar produced from cotton gin waste (CG700) and walnut shells (WS800) to remove four pharmaceuticals (ACT, SPY, IBP, and DCT) from aqueous solution. Physico-chemical properties of the biochars were characterized by Brunauer-Emmett-Teller (BET) analysis, scanning electron microscopy (SEM), Fourier Transform Infrared Spectroscopy (FT-IR), and zeta potential. The increased pyrolysis temperature during the production of WS800 led to an increase in the specific surface area and increased dehydration of the biochar represented by the loss of the OH-group. Fixed-bed column experiments were performed to determine the difference in removal efficiency between the biochars and elucidate the effects of biochar properties on the adsorption capacity for the pharmaceuticals of interest. Results showed that CG700 had a greater affinity for removing DCT (99%) and IBP (50%), while WS800 removed 72% of SPY and 68% of ACT after 24 h. Adsorption was influenced by the solution pH, surface area, net charge, and functional groups of the biochars. The mechanisms for removal included pore filling and diffusion, hydrophobic interactions, hydrogen bonding, and π-π electron donor acceptor interactions. To conduct predictive modeling of the column breakthrough curves, the Thomas, Adams-Bohart, and Yoon-Nelson models were applied to the experimental data. Results demonstrated that these models generally provided a poor fit for the description of asymmetrical breakthrough curves. Overall, the results demonstrate that biochars from cotton gin waste and walnut shells could be used as cost-effective, environmentally friendly alternatives to activated carbon for the removal of pharmaceuticals from aqueous solutions.

Low temperature pyrolytic biochar is a preferred choice for sulfonamide-Cu(II) contaminated soil remediation in tropical climate region.

Biochar is getting increasing consideration for eco-friendly soil amendment and environmental remediation. Once added to the soil, biochar would undergo the natural ageing process, affecting its physicochemical properties and, as a result, the adsorption and immobilization of pollutants in the water and soil. To evaluate the high/low temperature pyrolyzed biochar performance on complex contaminants and the effect of climate ageing, the batch experiments were conducted on the adsorption of the pollutants of antibiotics sulfapyridine (SPY) and a typical coexisting heavy metal Cu2+ as one or binary system on low/high pyrolytic temperature biochars before and after the simulated tropical climate and frigid climate region ageing treatment. The results showed that high-temperature ageing could enhance the SPY adsorption in biochar-amended soil. The SPY sorption mechanism was fully elucidated, and the result confirmed that H-bonding was the dominant role in biochar-amended soil, and π-π electron-donor-acceptor (EDA) interaction and micro-pore filling was another factor for SPY adsorption. This study could lead to the conclusion that low-temperature pyrolytic biochar is a better option for sulfonamide-Cu(II) contaminated soil remediation in tropical regions.

Biotic transformation products of sulfonamides in environmental water samples: High-resolution mass spectrometry-based tentative identification by a suspect screening approach.

The presence of pharmaceuticals in the aquatic environment is mainly due to their release from the effluents of the wastewater treatment plants (WWTPs), which are unable to completely remove them and their transformation products (TPs). Sulfonamides (SAs) are a synthetic antibacterial class used for the treatment of both human and animal infections; they have often been reported in surface water, thus contributing to the antibiotic resistance emergency. Monitoring SA TPs should be important as well because they could still exert some pharmaceutical activity; however, many TPs are still unknown since several transformation processes are possible (e. g. human and animal metabolism, WWTP activities, environmental factors etc.). In this work, three of the most used SAs, i.e., sulfamethoxazole (SMX), sulfapyridine (SPY), and sulfadiazine (SDZ), were incubated for 20 days in a batch reactor with activated sludge under controlled conditions. Then, the water sample was extracted and analyzed by ultra-high performance liquid chromatography-high resolution mass spectrometry in the data dependent acquisition (DDA) mode. Starting from the literature data, the possible transformation pathways were studied, and for each SA, a list of TPs was hypothesized and used for the identification. The raw data files were processed with Compound Discoverer, and 44 TPs (18, 13, and 13 TPs for SMX, SPY, and SDZ, respectively), including multiple TPs, were manually validated. To overcome the limitation of the DDA, the identified TPs were used in an inclusion list to analyze WWTP samples by a suspect screening approach. In this way, 4 SMX TPs and 5 SPY TPs were tentatively identified together with their parent compounds. Among these TPs, 5 of 9 were acetylated forms, in agreement with previous literature reporting that acetylation is the predominant SA transformation.

Predicting combined antibacterial activity of sulfapyridine and its transformation products during sulfapyridine degradation.

Antibiotics have strong antibacterial activity, even trace antibiotics can greatly inhibit the pollutant degradation efficiency. In order to effectively improve the pollutant degradation efficiency, it was hence of great significance to explore sulfapyridine (SPY) degradation and the mechanism of antibacterial activity. This study selected SPY as the research object, of which the trend of SPY concentration through hydrogen peroxide (H2O2), potassium peroxydisulfate (PDS) and sodium percarbonate (SPC) and resultant antibacterial activity at pre-oxidation was examined. The combined antibacterial activity (CAA) of SPY and its transformation products (TPs) was further analyzed. The SPY degradation efficiency reached more than 90 %. However, the degradation efficiency of antibacterial activity was between 40-60 %, and the mixture's antibacterial activity was difficult to be removed. The antibacterial activity of TP3, TP6 and TP7 was higher than that of SPY. TP1, and TP8 and TP10 were more prone to synergistic reaction with other TPs. The antibacterial activity of binary mixture gradually changed from synergism to antagonism as binary mixture concentration increased. The results provided a theoretical basis for the efficient degradation of antibacterial activity of the SPY mixture solution.

Spatiotemporal distribution of veterinary and human drugs and its predictability in Japanese catchments.

Little is known about the predictability of mass flows of veterinary drugs in Asian catchments, where effluent from livestock farms is a major source. We therefore conducted this study to understand the applicability and limitations of a population-based emission model, which assumed usage of veterinary and human drugs to be evenly distributed over the national livestock or human population throughout the year, and sources to be effluent discharges at livestock farms, households, and sewage treatment plants in Japanese catchments. We monitored five veterinary drugs (lincomycin, sulfamonomethoxine, tiamulin, tylosin, and tilmicosin), two human and livestock drugs (sulfamethoxazole and trimethoprim), two human drugs (carbamazepine and clarithromycin), and a metabolite (sulfapyridine) of a human drug once a month over 2 years in eight Japanese rivers which have active livestock farming in their catchments. Mass flows of carbamazepine and sulfapyridine were stable, while those of veterinary drugs fluctuated widely, especially sulfamonomethoxine and tilmicosin, whose 25 %-100 % ranges averaged 1.5 and 1.2 log units, respectively, attributable mainly to their usage patterns. The model accurately predicted mean mass flows of carbamazepine in the rivers with errors of <±0.3 log unit. Although it slightly to moderately overestimated those of the other four human-related compounds, the incorporation of an empirical correction factor, determined to minimize mean absolute error (MAE) among the rivers, substantially lowered their MAEs to <0.23 log units. However, the MAEs of the five veterinary drugs were as high as 0.42 (sulfamonomethoxine) to 0.60 (tiamulin) log units even with the coefficient, likely due mainly to the spatial distribution of their usage per capita. So as not to overlook spatiotemporal elevation of risks of veterinary drugs, a stochastic method should be applied in their management. This is the first study to assess the use of spatiotemporal homogeneity in usage per capita of veterinary drugs in Asian catchments.

Broad-Specificity Aptamer of Sulfonamides: Isolation and Its Application in Simultaneous Detection of Multiple Sulfonamides in Fish Sample.

Sulfonamide antibiotics (SAs) are widely used in animal husbandry and aquaculture, and the excess residues of SAs in animal-derived foods will harm the health of consumers. In reality, various SAs were alternately used in animal husbandry and aquaculture, and thus, it is urgent need to develop simple and high-throughput methods for simultaneously detecting multiple SAs or groups of SAs in order to realize rapid screening of total SAs residues in animal-derived foods. We herein isolated a broad-specificity aptamer for SAs by using a multi-SAs systematic evolution of ligands by exponential enrichment (SELEX) strategy. The isolated broad-specificity aptamer has a higher binding affinity to five different SAs including sulfaquinoxaline (SQ), sulfamethoxypyridazine (SMPZ), sulfametoxydiazine (SMD), sulfachloropyridazine (SCP), and sulfapyridine (SPD) and, thus, can be used as a bioreceptor for developing various high-throughput methods for the simultaneous detection or rapid screening of above five SAs. Based on the isolated broad-specificity aptamer and Cy7 (diethylthiatricarbocyanine) displacement strategy, a colorimetric aptasensor was developed for the simultaneous detection of SQ, SMPZ, SMD, SCP, and SPD with a visual detection limit of 2.0-5.0 µM and a spectrometry detection limit of 0.2-0.5 µM. The colorimetric aptasensor was successfully used to detect SQ, SMPZ, SMD, SCP, and SPD in fish muscle with a recovery of 82%-92% and a RSD (n = 5) < 7%. The success of this study provided a promising bioreceptor for developing various high-throughput methods for on-site rapid screening of multiple SAs residues, as well as a simple method for the rapid and cost-effective screening of total SQ, SMPZ, SMD, SCP, and SPD in seafood.

Fixed bed column performance of Al-modified biochar for the removal of sulfamethoxazole and sulfapyridine antibiotics from wastewater.

In this study, biochar derived from bamboo pretreated with aluminum salt was synthesized for the removal of two sulfonamide antibiotics, sulfamethoxazole (SMX) and sulfapyridine (SPY), from wastewater. Batch sorption experiments showed that Al-modified bamboo biochar (Al-BB-600) removed both sulfonamides effectively with the maximum sorption capacity of 1200-2200 mg/kg. The sorption mechanism was mainly controlled by hydrophobic, π-π, and electrostatic interactions. Fixed bed column experiments with Al-modified biochar packed in different dosages (250, 500 and 1000 mg) and flow rates (1, 2 and 4 mL/min) showed the dosage of 1000 mg and flow rate of 1 mL/min performed the best for the removal of both SMX and SPY from wastewater. Among the breakthrough (BT) models used to evaluate the fixed bed filtration performance of Al-BB-600, the Yan model best described the BT behavior of the two sulfonamides, suggesting that the adsorption process involved multiple rate-liming factors such as mass transfer at the solid surface and diffusion Additionally, the Bed Depth Service Time (BDST) model results indicated that Al-BB-600 can be efficiently used in fixed bed column for the removal of both SMX and SPY in scaled-up continuous wastewater flow operations. Therefore, Al-modified biochar can be considered a reliable sorbent in real-world application for the removal of SMX and SPY from wastewater.

Peroxymonosulfate activation using heterogeneous catalyst Sr2FeO4 coated on SBA-15 for efficient degradation of antibiotic sulfapyridine.

It is significant to explore the advanced oxidation process (AOP) for antibiotic degradation. Herein, a peroxymonosulfate (PMS) activator, Sr2FeO4/SBA-15 (SFS) heterogeneous catalyst, was synthesized by in situ growth of Sr2FeO4 on the surface of SBA-15. In SFS/PMS catalytic system, Sr atom provided electrons to Fe(II) ↔Fe(III) ↔Fe(II) redox cycle through Sr-O-Fe bonds for PMS activation. The SFS catalyst could activate PMS to generate a free radical coexistence system, including sulfate radical (SO4∙-) and hydroxyl radicals (∙OH). The catalyst possessed high catalytic activity and high stability. The degradation efficiency of sulfapyridine (SAD) over the SFS/PMS catalytic system could reach 99.0% after 90 min reaction. After the 5th reuse, the degradation efficiency of SAD was still more than 94.0%, and the phase structure of the catalyst did not alter. The low ion leaching concentration would be more conducive to reuse and avoiding secondary pollution, in comparison to homogeneous catalysts. This catalyst can be widely applied to organic wastewater treatment.-->.

Trans ethosomal hybrid composites of naproxen-sulfapyridine in hydrogel carrier: anti-inflammatory response in complete Freund's adjuvant induced arthritis rats.

Current treatment for Rheumatoid arthritis (RA) utilizes Disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs or its combination, to decrease joint inflammation. In the present study, naproxen (NAP) and sulfapyridine (SULF) ethosomes were prepared by a thin-film hydration technique using PL90G and cholesterol, later crosslinked with carbopol®934. The ethosomes and ethosomal hydrogel were evaluated for rheological properties, physico-chemical analysis, in vitro and in vivo study. The results show, NAP and SULF ethosomes exhibited an average vesicle size between 251.1 ± 1.80-343.5 ± 3.23 nm and 269.0 ± 1.17-358.8 ± 1.22 nm, respectively, with good stability (zeta potential > 30 mV) and polydispersity index. Differential scanning calorimeter and Fourier transform infrared studies reveal no significant changes in the drug properties of ethosomes. Transmission electron microscopy analysis discloses spherical shape vesicles below 200 nm. The entrapment efficiency of NAP and SULF ethosomes was above 66%, and NAP-SULF ethosomes-hydrogel (EH) exhibited a sustained release effect (>8 h). In vivo studies on NAP-SULF EH shows significant inhibition of inflammation (84.63%), with less paw volume (0.1935 ± 0.08 ml) on induced arthritis Albino Wistar rats, (p < .01). NAP-SULF EH was stable at 25 °C ± 0.5 for 3-months. To conclude, a hybrid composite of NAP-SULF in hydrogel carrier prevents inflammation effectively, and could be novel for trans delivery of drugs in RA.

Fail-safe nano-formulation of prodrug of sulfapyridine: Preparation and evaluation for treatment of rheumatoid arthritis.

Aim of the present study was to give a second life to the long-abandoned drug, sulfapyridine (SP) for its anti-arthritic potential by design of nano-vesicular delivery system. For this, intra-articular delivery of its liposomal formulation was tried. As the prepared formulation exhibited rapid drug leakage, an arthritis responsive prodrug of SP showing lability towards synovial enzymes was synthesized to exploit the over-expression of arthritis specific enzymes. Prodrug (SP-PD) exhibited better retention in liposomes as compared to the drug, preventing its escape from synovium. Hydrolysis of SP-PD in human plasma and synovial fluid indicated its high susceptibility to enzymes. The liposomes of SP-PD exhibited larger mean size, less PDI and higher zeta potential as compared to those for SP liposomes. In arthritic rats, prodrug liposomes were found to reverse the symptoms of inflammation, including the levels of biochemical markers. Liposomes of bio-responsive prodrug, therefore, offer a revolutionary approach in the treatment of rheumatoid arthritis.

Development of Novel Magneto-Biosensor for Sulfapyridine Detection.

In this work, we report the development of a highly sensitive biosensor for sulfapyridine detection based on an integrated bio micro-electromechanical system (Bio-MEMS) containing four gold working electrodes (WEs), a platinum counter electrode (CE), and a reference electrode (RE). Firstly, the cleaned WEs were modified with 4-aminophenylacetic acid (CMA). Then, (5-[4-(amino)phenylsulfonamide]-5-oxopentanoic acid (SA2BSA) was immobilized onto the transducers surface by carbodiimide chemistry. The analyte was quantified by competitive detection with SA2BSA immobilized on the WE toward a mixture of Ab155 antibody (with fixed concentration) and sulfapyridine. In order to obtain a highly sensitive biosensor, Ab155 was immobilized onto magnetic latex nanoparticles surface to create a 3D architecture (Ab-MLNp). Using electrochemical impedance spectroscopy (EIS), we investigated the influence of the Ab-MLNp on the sensitivity of our approach. The optimized system was analyzed, as competitive assay, with different concentrations of sulfapyridine (40 µM, 4 µM, and 2 nM) and with phosphate buffer solution. From data fitting calculations and graphs, it was observed that the EIS showed more linearity when Ab-MLNp was used. This result indicates that the magnetic latex nanoparticles increased the sensitivity of the biosensor.

High-Performance Liquid Chromatography and Liquid Chromatography/Mass Spectrometry Studies on Stress Degradation Behavior of Sulfapyridine and Development of a Validated, Specific, Stability-Indicating HPLC Assay Method.

The objective of the current investigation was to develop a simple, rapid, and stability-indicating high-performance liquid chromatography method and to study the degradation behavior of sulfapyridine (SP) under different International Conference on Harmonization (ICH)-recommended conditions. The chromatographic method was developed using C18 (250 × 4.6 mm, 5 µ) column, and mobile phase consisting of acetonitrile-0.1% formic acid (30:70 v/v) at ambient temperature, at a flow rate of 1 mL/min. The elution was monitored at 265 nm using a photodiode array detector. The developed method was subsequently validated as per ICH Q2 (R1) guidelines. The retention time of SP was observed as 4.56 min with the linearity range between 2 to 10 µg/mL. Limit of detection and limit of quantitation for SP were 0.115 and 0.35 µg/mL, respectively. Forced degradation studies were carried out on bulk samples of SP using prescribed acidic, basic, oxidative, thermal, and photolytic conditions. Extent of degradation in 0.1 M hydrochloric acid and under photolytic conditions was found to be 21.56% and 28.57%, respectively. The degradation products formed in stress conditions were identified by liquid chromatography-mass spectrometry (LC-MS). The utility of the method was verified by quantification of SP in different laboratory-made pharmaceutical preparations. The proposed method could be successfully used to quantify SP in different pharmaceutical dosage forms.

Synthesis of sulpha drug based hydroxytriazene derivatives: Anti-diabetic, antioxidant, anti-inflammatory activity and their molecular docking studies.

Herein, we report synthesis, characterization, anti-diabetic, anti-inflammatory and anti-oxidant activities of hydroxytriazenes derived from sulpha drugs, namely sulphanilamide, sulphadiazine, sulphapyridine and sulphamethazine. Before biological screening of the compounds, theoretical prediction using PASS was done which indicates probable activities ranging from Pa (probable activity) values 65-98% for anti-inflammatory activity. As per the predication, experimental validation of some of the predicted activities particularly anti-diabetic, anti-inflammatory and anti-oxidant was done. Anti-diabetic activities have been screened using two methods namely α-amylase and α-glucosidase inhibition method and IC50 values were ranging from 66 to 260 and 148 to 401 µg/mL, while for standard drug acarbose the values were 12 µg/mL and 70 µg/mL, respectively. Docking studies have also been done for antidiabetic target pancreatic alpha amylase. The molecular docking studies in α-amylase enzyme reveal that the middle phenyl ring of all the compounds mainly occupies in the small hydrophobic pocket formed by the Ala198, Trp58, Leu162, Leu165 and Ile235 residues and sulphonamide moiety establish H-bond interaction by two water molecules. Further, anti-inflammatory activity has been evaluated using carrageenan induced paw-edema method and results indicate excellent anti-inflammatory activity by hydroxytriazenes (71 to 97%) and standard drug diclofenac 94% after 4 h of treatment. Moreover, antioxidant effect of the compounds was tested using DPPH and ABTS methods. All the compounds displayed good results (24-488 µg/mL) against ABTS radical and many compounds are more active than ascorbic acid (69 µg/mL) while all other compounds showed moderate activity against DPPH radical (292-774 µg/mL) and ascorbic acid (29 µg/mL). Thus, the studies reveal potential of sulfa drug based hydroxytriazenes as candidates for antidiabetic, anti-inflammatory and antioxidant activities which have been experimentally validated.

Ball milled biochar effectively removes sulfamethoxazole and sulfapyridine antibiotics from water and wastewater.

Release of antibiotics into the environment, which often occurs downstream of wastewater treatment plants, poses a human health threat due to the potential development of bacterial antibiotic resistance. In this study, laboratory experiments were conducted to evaluate the performance of ball milled biochar on the removal of two sulfonamide antibiotics, sulfamethoxazole (SMX) and sulfapyridine (SPY) from water and wastewater. Aqueous batch sorption experiment using both pristine and ball milled biochar derived from bagasse (BG), bamboo (BB) and hickory chips (HC), made at three pyrolysis temperatures (300, 450, 600 °C), showed that ball milling greatly enhanced the SMX and SPY adsorption. The 450 °C ball milled HC biochar and BB biochar exhibited the best removal efficiency for SMX (83.3%) and SPY (89.6%), respectively. A range of functional groups were produced by ball milling, leading to the conclusion that the adsorption of sulfonamides on the biochars was controlled by multiple mechanisms including hydrophobic interaction, π-π interaction, hydrogen bonding, and electrostatic interaction. Due to the importance of electrostatic interaction, SMX and SPY adsorption was pH dependent. In laboratory water solutions, the Langmuir maximum adsorption capacities of SMX and SPY reached 100.3 mg/g and 57.9 mg/g, respectively. When tested in real wastewater solution, the 450 °C ball milled biochar still performed well, especially in the removal of SPY. The maximum adsorption capacities of SMX and SPY in wastewater were 25.7 mg/g and 58.6 mg/g, respectively. Thus, ball milled biochar has great potential for SMX and SPY removal from aqueous solutions including wastewater.

Nanostructured hybrid surface enhancement Raman scattering substrate for the rapid determination of sulfapyridine in milk samples.

The fabrication of surface-enhanced Raman spectroscopy (SERS) substrates, which can offer the advantages of strong Raman signal enhancement with good reproducibility, is still a challenge for practical applications. In this work, a simple and reproducible SERS substrate combining the properties of multi-walled carbon nanotubes (MWCNTs) and gold nanoparticles (AuNPs), is proposed for the determination and quantification of sulfapyridine in milk samples with a concentration range of 10-100 ng mL-1. The Raman signals of sulfapyridine is enhanced at factor of 4394. The procedure presented is capable of detecting and quantifying small quantities of sulfapyridine without implying any preconcentration step, just using an affordable and portable Raman spectrometer. The precision, in terms of repeatability and inter and intermediate precision, was lower than 8% in all cases.