Validation of a rapid and economical RP-HPLC method for simultaneous determination of metformin hydrochloride and sitagliptin phosphate monohydrate: Greenness evaluation using AGREE score.

Reported high performance liquid chromatographic (HPLC) methods for estimating metformin hydrochloride (MET) and sitagliptin phosphate monohydrate (SIT) are either laborious or contain higher proportions of organic solvents in mobile phase, thus presenting exorbitant procedures. So, a rapid, significantly more economical and eco-friendly HPLC method for synchronized analysis of both drugs was aimed to develop and validate in current study. Analytical evaluation was executed on Shimadzou⌖ C18 column (250mm × 4.6mm, 5µm) using acidified water and methanol 60:40 (v/v) as mobile phase at a flow of 1mL/min; while peaks were detected at 260nm at 25°C. Resultant values of accuracy, precision, linearity, limit of detection (LOD), limit of quantification (LOQ), robustness and specificity depicted that the method was validated in accordance with the ICH Guidelines. The approximate retention time for MET and SIT were 1.96 and 3.70 min, correspondingly. The greenness score of the developed method was evaluated using AGREE software and was found better (0.81) as compared with the methods reported (<0.8). Conclusively, the developed method was time saving, economical, rapid, robust, rugged, precise, accurate and found to be applicable for simultaneous determination of MET and SIT in commercial tablets.

Initiatives to broaden safety concerns in anaesthetic practice: The green operating room.

The health sector is a major contributor to climate change through its large carbon footprint. Hospitals are highly energy and resource intensive. Operating rooms (ORs) contribute to a major part of these emissions because of anaesthetic gases, energy-intensive equipment and waste. Besides initiatives aimed to mitigate hospitals' climate footprints, health care professionals need to be involved in this process by changing their professional and personal behaviours without compromising the quality of care. Education on metrics (greenhouse gases), concepts (life cycle) and strategies to reduce the health care footprint would help professionals to commit themselves to the issue. The 5R's rule (reduce, reuse, recycle, rethink and research) used to promote an environmentally friendly way of life can be applied to the medical field and especially to the operating room and anaesthesia. When applied in the ORs, these strategies help question the use of disposable devices, attires and packaging, as well as our professional and personal behaviour. Greening the ORs requires the engagement of all professionals as well as other departments (pharmacy, hygiene) and management. Economic and social co-benefits are expected from this process.

Medical and cytotoxicity effects of green synthesized silver nanoparticles using Achillea millefolium extract on MOLT-4 lymphoblastic leukemia cell line.

Green chemistry, which aims at the development of efficient methods for the synthesis of nanoparticles, is a relatively new emerging field of nanotechnology, which has economic and environment-friendly benefits over chemical and physical processes. The present work was carried out to develop silver nanoparticles (Ag-NPs) using the plant (Achillea millefolium or yarrow) aqueous extract as both a reducing and capping agent under the green synthesis method. Characterization of synthesized Ag-NPs was done using IR spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), and ultraviolet-visible (UV-vis). The UV-vis spectrum showed the maximum absorbance at around 440-470 nm, which suggested the formation of green synthesized Ag-NPs. The morphological study demonstrated that the Ag-NPs were spherical in shape with an average size of 22.4 ± 7.4 nm. The antimicrobial activities of Ag-NPs against Fusarium and Aspergillus niger species of fungal and Escherichia coli species of bacteria were investigated through the disc diffusion and well-diffusion method using their zone of inhibition. The cytotoxicity effect of Ag-NPs on cell lines MOLT-4 was evaluated by using MTT assay. These nanoparticles showed remarkable antimicrobial activity against bacterias and fungus in low concentration. The cytotoxicity studies showed that IC50 of green synthesized Ag-NPs was 0.011 µm in comparison to 1.8 for Cisplatin which more active than anticancer drug for MOLT-4 cell line. The results showed that the green synthesized Ag-NPs are expected to have notable applications and can be potentially useful in pharmaceutical and biomedical applications.

Green synthesis and environmental application of iron-based nanomaterials and nanocomposite: A review.

Green chemistry has been proven to be an efficient route for nanoparticle synthesis. Plant extract based green synthesis of various nanoparticles is extensively studied since the last decade. This paper "Green synthesis and environmental application of Iron-based nanomaterials and nanocomposite: A review" unveils all the possible greener techniques for the synthesis of iron-based nanoparticles and nanocomposites. The use of different plant sources, microorganisms, and various biocompatible green reagents such as biopolymers, cellulose, haemoglobin, and glucose for the synthesis of iron nanoparticles reported in the last decade are summarized. The microwave method, along with hydrothermal synthesis due to their lower energy consumption are also been referred to as a green route. Apart from different plant parts, waste leaves and roots used for the synthesis of iron nanoparticles are extensively briefed here. This review is thus compact in nature which covers all the broad areas of green synthesis of iron nanoparticles (NPs) and iron-based nanocomposites. Detailed discussion on environmental applications of the various green synthesized iron NPs and their composites with performance efficiency is provided in this review article. The advantages of bimetallic iron-based nanocomposites over iron NPs in various environmental applications are discussed in detail. The hazards and toxic properties of green synthesized iron-based NPs are compared with those obtained from chemical methods. The prospects and challenges section of this article provides a vivid outlook of adapting such useful technique into a more versatile process with certain inclusions which may encourage and provide a new direction to future research.

Green conventional and first-order derivative fluorimetry methods for determination of trimebutine and its degradation product (eudesmic acid). Emphasis on the solvent and pH effects on their emission spectral properties.

In this report, the fluorescence properties of the antimuscarinic drug trimebutine maleate (TRB) were fully studied and characterized. TRB exhibited intrinsic fluorescence that is greatly dependent on the local environmental factors including the solvent nature and the pH. Yet, its fluorescence was not significantly influenced by the existence of some surface active agents and polymer. The outcomes of this investigation verified that TRB fluorescence emission is intense in ethanol: 1.0 M aqueous acetic acid (9:1, v/v) with emission maxima at 357 nm and excitation maxima at 270 nm. Whereas, going towards higher pH causes fluorescence quenching. These conditions permitted ultrasensitive fluorimetric determination of TRB over the concentration range of 2.00-1500.0 ng/mL with a lower detection limit of 0.40ng/mL Application for the determination of TRB in tablets, ampoule and suspension was successfully achieved with %recoveries ranged between 98.21-100.17%. Furthermore, a first order derivative fluorimetric method was validated for resolving and simultaneous determination of TRB and its degradation product and impurity, eudesmic acid (EUA) making use of the pH-mediated fluorescence spectral shift of EUA. An ethanolic solution containing acetate buffer (pH 5.3) was used for this goal with excitation at 255 nm and measurement of the first order derivative peak amplitudes at respective zero-crossing points of 375 and 351 nm over the corresponding concentration ranges of 20.00-500.00 and 10.00-300.00 ng/mL for TRB and EUA, respectively. The two methods were assessed regarding greenness and eco-friendship by the National Environmental Methods Index and analytical eco-scale score approaches which confirmed their excellent greenness and safety.

Analytical Eco-Scale for Assessing the Greenness of a Developed Potentiometric Method for Lomefloxacin Hydrochloride Determination in its Different Dosage Forms, Plasma, and Dissolution Medium.

Background: Traditional methods for Lomefloxacin hydrochloride (LOM) determination involve pretreatment steps, which extend analysis time and use hazardous chemicals. Objective: The ability to provide a rapid route without sample pretreatment for quantitative determination of compounds via a low-cost instrument is a challenging task. In this work, a simple potentiometric method was developed to determine the antibacterial LOM via in-house fabricated ion selective electrodes. Methods: Different sensors were fabricated using a poly vinyl chloride-based membrane, potassium tetrakis(4-chlorophenyl) borate as a cation exchanger, and 2-Nitrophenyl octyl ether as a plasticizer (sensor 1). To increase the selectivity of sensor 1, a selective molecular recognition component 2-hydroxypropyl-ß-cyclodextrin was used as ionophore (sensor 2). Results: The proposed method was validated according to International Union of Pure and Applied Chemistry recommendations, in which the proposed sensors show a linear dynamic range from 1 × 10-5 to 1 × 10-2 mol/L, with Nernstian slopes of 55.829 and 58.229 mV/decade for sensors 1 and 2, respectively. It was applied to determine LOM in bulk powder, in different dosage forms, and in plasma with no sample pretreatment. Also, the suggested method can be used as a green, in-line bench top real-time analyzer for in-process monitoring of LOM release from its tablets, under U.S. Food and Drug Administration dissolution regulations, with clear discrimination from common excipients. Results obtained by the proposed potentiometric method were compared with those obtained by a reported HPLC method. Conclusions: The proposed method is considered as a perfect alternative to traditional reported methods for LOM determination.

Environment-Friendly Practices in Operating Rooms in Turkey.

BACKGROUND: Environment-friendly practices refer to decreasing energy consumption, using resources carefully and sustainably, and reducing environmental pollution. An environment-friendly hospital is defined as a hospital where energy is saved, carbon emissions are decreased, and productivity and quality are increased. Operating rooms (ORs) account for most wastes generated daily by hospitals. Thus, adopting environment-friendly healthcare practices in ORs will have a positive impact on the environment. PURPOSE: The aim of this study was to identify and recommend environment-friendly practices that are feasible for implementation in ORs in Turkey. METHODS: Data on the environment-friendly practices that are currently being practiced in the ORs of hospitals in Izmir Province were collected using face-to-face interviews with nurses who were in charge of ORs in Izmir Province. The interviews were conducted using an OR identification form and Greening the OR Checklist. The study population included all of the hospitals in Izmir Province, and the study sample included 18 ORs in the 11 hospitals that consented to take part in the research. Permission to conduct this research was obtained from the ethics committee of the nursing school as well as from the participating hospitals where the study was conducted. RESULTS: The hospitals included in the study had, on average, 7.44 ± 7.32 ORs, each of which employed an average of 16.83 ± 17.16 nurses. Four fifths (83.3%) of the ORs always monitored their wastes, and 88.9% gave their batteries to recyclers. In addition, 72.2% renewed their surgical sets to reduce excessive use of materials, and 72.2% preferred using reusable materials instead of single-use materials in their surgical sets. However, 66.7% of the ORs had no environmental team, 93% did not use an environmentally safe surface cleaner, 83.3% did not use sensor controls on lights, and 66.7% did not use LED lights. CONCLUSIONS: Although most hospitals did not have a special team to recommend and enforce environment-friendly procedures, the OR nurses did their best to protect the environment.

Optimisation of green synthesis of MnO nanoparticles via utilising response surface methodology.

This study concerns the optimisation of green synthesis of manganese oxide nanoparticles (MnO NPs) with Dittrichia graveolens (L.) extract via response surface methodology (RSM). Central composite design was used to evaluate the effect of pH, time, and the extract to the metal ratio on the synthesised nanoparticles (NPs). Nine runs were designed to investigate the effect of each parameter while NPs were synthesised under different conditions. Considering the p-values (p-value < 0.05), it is indicated that the extract to the metal ratio was the most effective parameter. The synthesised NPs were characterised using UV-vis. Synthesis of the NPs by polyphenolic compounds of green reducing agent and their stabilisation by curcumin was confirmed by Fourier transform infrared spectra and the surface morphology of the spherical MnO NPs was studied by field-emission scanning electron microscopy and transmission electron microscope techniques. The present researchers claimed the optimal condition as follows: time = 56.7 min, pH = 7.2, and the extract to the metal ratio = 87.9 v/v. MnO NPs at optimum condition were then employed for degradation of industrial dyes and they showed high dye degradation activity against Rhodamine B and light green dye. The average size of the synthesised MnO NPs at optimal condition was claimed to be nearly 38 nm.

Enhancement of fermentative hydrogen production from Spirogyra sp. by increased carbohydrate accumulation and selection of the biomass pretreatment under a biorefinery model.

In this work, hydrogen (H2) was produced through the fermentation of Spirogyra sp. biomass by Clostridium butyricum DSM 10702. Macronutrient stress was applied to increase the carbohydrate content in Spirogyra, and a 36% (w/w) accumulation of carbohydrates was reached by nitrogen depletion. The use of wet microalga as fermentable substrate was compared with physically and chemically treated biomass for increased carbohydrate solubilisation. The combination of drying, bead beating and mild acid hydrolysis produced a saccharification yield of 90.3% (w/w). The H2 production from Spirogyra hydrolysate was 3.9 L H2 L-1, equivalent to 146.3 mL H2 g-1 microalga dry weight. The presence of protein (23.2 ± 0.3% w/w) and valuable pigments, such as astaxanthin (38.8% of the total pigment content), makes this microalga suitable to be used simultaneously in both food and feed applications. In a Spirogyra based biorefinery, the potential energy production and food-grade protein and pigments revenue per cubic meter of microalga culture per year was estimated on 7.4 MJ, US $412 and US $15, respectively, thereby contributing to the cost efficiency and sustainability of the whole bioconversion process.

The Molecular Design Research Network.

Herein, we provide an overview of a research network that is aimed at fostering interdisciplinary collaboration between chemists and toxicologists with the goal of rationally designing safer commercial chemicals. The collaborative is the Molecular Design Research Network (MoDRN) that was created in 2013 with funding from the EPA-National Science Foundation Networks for Sustainable Molecular Design and Synthesis (NSMDS) program. MoDRN is led by 4 universities, Baylor University, University of Washington, The George Washington University, and Yale University. The overarching goal of the network is to enable and empower the design of safer chemicals based on the fourth Principle of Green Chemistry that states, "chemical products should be designed to preserve efficacy of function while minimizing toxicity."

The Need for, and the Role of the Toxicological Chemist in the Design of Safer Chemicals.

During the past several decades, there has been an ever increasing emphasis for designers of new commercial (nonpharmaceutical) chemicals to include considerations of the potential impacts a planned chemical may have on human health and the environment as part of the design of the chemical, and to design chemicals such that they possess the desired use efficacy while minimizing threats to human health and the environment. Achievement of this goal would be facilitated by the availability of individuals specifically and formally trained to design such chemicals. Medicinal chemists are specifically trained to design and develop safe and clinically efficacious pharmaceutical substances. No such formally trained science hybrid exists for the design of safer commercial (nonpharmaceutical) chemicals. This article describes the need for and role of the "toxicological chemist," an individual who is formally trained in synthetic organic chemistry, biochemistry, physiology, toxicology, environmental science, and in the relationships between structure and commercial use efficacy, structure and toxicity, structure and environmental fate and effects, and global hazard, and trained to integrate this knowledge to design safer commercially efficacious chemicals. Using examples, this article illustrates the role of the toxicological chemist in designing commercially efficacious, safer chemical candidates.

Analytical Eco-Scale for Assessing the Greenness of a Developed RP-HPLC Method Used for Simultaneous Analysis of Combined Antihypertensive Medications.

In the past few decades the analytical community has been focused on eliminating or reducing the usage of hazardous chemicals and solvents, in different analytical methodologies, that have been ascertained to be extremely dangerous to human health and environment. In this context, environmentally friendly, green, or clean practices have been implemented in different research areas. This study presents a greener alternative of conventional RP-HPLC methods for the simultaneous determination and quantitative analysis of a pharmaceutical ternary mixture composed of telmisartan, hydrochlorothiazide, and amlodipine besylate, using an ecofriendly mobile phase and short run time with the least amount of waste production. This solvent-replacement approach was feasible without compromising method performance criteria, such as separation efficiency, peak symmetry, and chromatographic retention. The greenness profile of the proposed method was assessed and compared with reported conventional methods using the analytical Eco-Scale as an assessment tool. The proposed method was found to be greener in terms of usage of hazardous chemicals and solvents, energy consumption, and production of waste. The proposed method can be safely used for the routine analysis of the studied pharmaceutical ternary mixture with a minimal detrimental impact on human health and the environment.

Quality Control of Widely Used Therapeutic Recombinant Proteins by a Novel Real-Time PCR Approach.

BACKGROUND: Existence of bacterial host-cell DNA contamination in biopharmaceutical products is a potential risk factor for patients receiving these drugs. Hence, the quantity of contamination must be controlled under the regulatory standards. Although different methods such as hybridization assays have been employed to determine DNA impurities, these methods are labor intensive and rather expensive. In this study, a rapid real-time PCR test was served as a method of choice to quantify the E. coli host- cell DNA contamination in widely used recombinant streptokinase (rSK) , and alpha interferon (IFN-α) preparations. METHODS: A specific primer pair was designed to amplify a sequence inside the E. coli 16S rRNA gene. Serial dilutions of DNA extracted from E. coli host cells, along with DNA extracted from Active Pharmaceutical Ingredients of rSK, and IFN-α samples were subjected to an optimized real-time PCR assay based on SYBR Green chemistry. RESULTS: The test enabled us to detect a small quantity of genomic DNA contamination as low as 0.0002 pg in recombinant protein-based drugs. For the first time, this study showed that DNA contamination in rSK and IFN-α preparation manufactured in Pasteur Institute of Iran is much lower than the safety limit suggested by the US FDA. CONCLUSION: Real-time PCR is a reliable test for rapid detection of host-cell DNA contamination, which is a major impurity of therapeutic recombinant proteins to keep manufacturers' minds on refining drugs, and provides consumers with safer biopharmaceuticals.

Procedure optimization for green synthesis of silver nanoparticles by aqueous extract of Eucalyptus oleosa.

The present study is dealing with the green synthesis of silver nanoparticles using the aqueous extract of Eucalyptus oleosa as a green synthesis procedure without any catalyst, template or surfactant. Colloidal silver nanoparticles were synthesized by reacting aqueous AgNO3 with E. oleosa leaf extract at non-photomediated conditions. The significance of some synthesis conditions such as: silver nitrate concentration, concentration of the plant extract, time of synthesis reaction and temperature of plant extraction procedure on the particle size of synthesized silver particles was investigated and optimized. The participations of the studied factors in controlling the particle size of reduced silver were quantitatively evaluated via analysis of variance (ANOVA). The results of this investigation showed that silver nanoparticles could be synthesized by tuning significant parameters, while performing the synthesis procedure at optimum conditions leads to form silver nanoparticles with 21nm as averaged size. Ultraviolet-visible spectroscopy was used to monitor the development of silver nanoparticles formation. Meanwhile, produced silver nanoparticles were characterized by scanning electron microscopy, energy-dispersive X-ray, and FT-IR techniques.

Comparison of two ionic liquid dispersive liquid-liquid microextraction approaches for the determination of benzoylurea insecticides in wastewater using liquid chromatography-quadrupole-linear ion trap-mass spectrometry: evaluation of green parameters.

Two dispersive liquid-liquid microextraction (DLLME) approaches including temperature-controlled ionic liquid dispersive liquid-liquid microextraction (TCIL-DLLME) and ultrasound-assisted ionic liquid dispersive liquid-liquid microextraction (US-IL-DLLME) were compared for the extraction of six benzoylurea insecticides (diflubenzuron, triflumuron, hexaflumuron, teflubenzuron, lufenuron and flufenoxuron) from wastewater samples prior to their determination by high-performance liquid chromatography with a hybrid triple quadrupole-linear ion trap-mass spectrometer (LC-QqLIT-MS/MS). Influential parameters affecting extraction efficiency were systematically studied and optimized and the most significant green parameters were quantified and compared. The best results were obtained using the US-IL-DLLME procedure, which employed the IL 1-octyl-3-methylimidazolium hexafluorophosphate ([C8MIM][PF6]) and methanol (MeOH) as extraction and disperser solvent, respectively. US-IL-DLLME procedure was fast, easy, low environmental toxicity and, it was also able to successfully extract all selected benzoylureas. This method was extensively validated with satisfactory results: limits of detection and quantification were in the range 0.5-1.0 ng L(-1) and 1.5-3.5 ng L(-1), respectively, whereas recovery rates ranged from 89 to 103% and the relative standard deviations were lower than 13.4%. The applicability of the method was assessed with the analysis of effluent wastewater samples from a wastewater treatment plant located in an agricultural zone of Almería (Spain) and the results indicated the presence of teflubenzuron at mean concentration levels of 11.3 ng L(-1). US-IL-DLLME sample treatment in combination with LC-QqLIT-MS/MS has demonstrated to be a sensitive, selective and efficient method to determine benzoylurea insecticides in wastewaters at ultra-trace levels.

Green toxicology.

Historically, early identification and characterization of adverse effects of industrial chemicals was difficult because conventional toxicological test methods did not meet R&D needs for rapid, relatively inexpensive methods amenable to small amounts of test material. The pharmaceutical industry now front-loads toxicity testing, using in silico, in vitro, and less demanding animal tests at earlier stages of product development to identify and anticipate undesirable toxicological effects and optimize product development. The Green Chemistry movement embraces similar ideas for development of less toxic products, safer processes, and less waste and exposure. Further, the concept of benign design suggests ways to consider possible toxicities before the actual synthesis and to apply some structure/activity rules (SAR) and in silico methods. This requires not only scientific development but also a change in corporate culture in which synthetic chemists work with toxicologists. An emerging discipline called Green Toxicology (Anastas, 2012) provides a framework for integrating the principles of toxicology into the enterprise of designing safer chemicals, thereby minimizing potential toxicity as early in production as possible. Green Toxicology`s novel utility lies in driving innovation by moving safety considerations to the earliest stage in a chemical`s lifecycle, i.e., to molecular design. In principle, this field is no different than other subdisciplines of toxicology that endeavor to focus on a specific area - for example, clinical, environmental or forensic toxicology. We use the same principles and tools to evaluate an existing substance or to design a new one. The unique emphasis is in using 21st century toxicology tools as a preventative strategy to "design out" undesired human health and environmental effects, thereby increasing the likelihood of launching a successful, sustainable product. Starting with the formation of a steering group and a series of workshops, the Green Toxicology concept is currently spreading internationally and is being refined via an iterative process.

Development of an innovative and "green" stir bar sorptive extraction-thermal desorption-gas chromatography-tandem mass spectrometry method for quantification of polycyclic aromatic hydrocarbons in marine biota.

There is a growing awareness of the need to reduce the negative impact of chemical analyses on the environment and to develop new eco-friendly and sustainable analytical methods without compromising performance. In this study, we developed a "green" analytical method enabling the accurate and simultaneous routine analysis of 21 polycyclic aromatic hydrocarbons (PAHs) in reduced quantities (100mg and 1g wet weight (WW)) of marine biota samples (fish muscle, mussel and oyster tissues) using alkaline digestion combined with stir bar sorptive extraction-thermal desorption-gas chromatography-tandem mass spectrometry (SBSE-GC-MS/MS). The innovative method provides good selectivity and specificity for most compounds. In 1gWW samples, limits of quantification (LOQs) ranged from 1 to 10µg/kgWW in fish muscle and from 0.5 to 10µg/kgWW in mussel tissue. The method enables most analytes to be quantified below the restrictive limits established by the European Commission (2 and 10µg/kgWW in fish muscle and bivalve mollusc, respectively). Higher LOQs were obtained in 100mgWW samples ranging from 1 to 50µg/kgWW. Recovery and linearity were assessed for all analytes. The results were satisfactory for most compounds with recoveries ranging from 94% to 117% in 1gWW mussel samples at spike concentration of 10ng/gWW with standard deviation not exceeding 12%. However, results confirmed that the SBSE efficiency is affected by the complexity of biological matrices, especially for high molecular weight compounds in lipid-rich mussel tissue. Because of the matrix effects, matrix-matched calibrations were carried out. Validation was performed using the standard reference material 1974c with recovery ranging from 71% to 119% except for naphthalene, anthracene and benzo(e)pyrene that were therefore not validated. Overall, the developed method meets analytical validation criteria for most compounds. Thanks to the combination of alkaline digestion and SBSE, which greatly simplifies sample treatment and limits solvent use to ethanol, the developed method followed most green analytical chemistry principles.