ABSTRACT
The scientific community has continued to pay particular attention to potentiometric sensors based on ion-selective membrane sensors as an energy-efficient, easy-to-use method suitable for microfabrication. To this end, potentiometric ion-selective sensors were used as an alternative green analytical instrument. Three distinct sensors relying on various ionophores were built and assessed. A cationic exchanger, tetra phenyl borate, was used in the polyvinyl chloride polymeric plasticized matrix using di octyl phthalate, where α, ß, and γ cyclodextrins were utilized as ionophores. A comparative potentiometric analysis was carried out using three ion-selective sensor designs: α, ß, and γ cyclodextrins sensors. ß-Cyclodextrin significantly reduced the detection limit and improved the discriminative performance of mebeverine hydrochloride (MBV) in the pharmaceutical dosage form over α- and γ-cyclodextrins in the presence of other interfering chemicals. Additionally, a significant connection was made between the practical perspective and a theoretical investigation based on computational research. Nernstian potentiometric results for the optimum sensor were obtained for MBV in the range of concentrations 1.0 × 10-2 to 1.0 × 10-6 M, its slope was -58.70 ± 0.12 mV per decade with lower detection limits 4.50 × 10-7 M. This computational molecular docking investigation clarified that the binding sites and modes were in good agreement with the experiment results. This investigation was applied to expect the interaction between MBV and the proposed sensors to ensure which ionophores were the best for MBV.
ABSTRACT
BACKGROUND: Low-dose aspirin (ASP) is prescribed to millions of people around the world as a secondary preventative strategy for the majority of significant cardiovascular events; however, it carries a substantial risk of gastric ulcer and bleeding. Cabpirin® tablets, which include low-dose ASP and vonoprazan fumarate (VON), are approved in Japan for the treatment of acid-related diseases in patients who require a low dose of ASP but are at risk of ASP-associated gastric ulcers. OBJECTIVE: This paper describes the first published quantitative analytical approaches for the determination of ASP and VON. METHOD: The normal ultraviolet absorption spectra of ASP and vonoprazan overlap significantly. The ratio spectra of the studied drugs were created and manipulated by ratio difference (RD) and first derivative of ratio spectra approaches. In the RD approach, the differences in the amplitude values between 229 and 283 nm enabled the quantitative analysis of ASP, and the differences in the amplitude values between 255 and 212 nm enabled the quantitative analysis of vonoprazan. In the first derivative of the ratio spectra approach, the created ratio spectra of each drug were transformed to the first-order derivative. ASP could be determined selectively at 237.40 nm without interference from vonoprazan. Moreover, vonoprazan could be determined selectively at 244 nm without interference from ASP. RESULTS: The applied approaches were validated according to the ICH guideline, with good results. Linear correlations were obtained for ASP and vonoprazan over concentration ranges of 2-25 and 1-10 µg/mL, respectively. CONCLUSIONS: The described methods were optimized, validated, and applied for determination of the studied drugs in the synthetic mixtures and in pharmaceutical tablets without interferences. HIGHLIGHTS: Two spectrophotometric ratio spectra manipulating approaches were developed for the determination of the ASP and vonoprazan in their pharmaceutical combination tablets.
Subject(s)
Aspirin , Fumarates , Humans , Spectrophotometry/methods , TabletsABSTRACT
BACKGROUND: Pain is a global, complex health problem that includes physical, emotional, and social components. The pain management process has many goals, including patient satisfaction, reducing clinical complications, and lowering costs. The physician describes pain medications in terms of the proven cause and classification of the severity of the pain. The combination of celecoxib and tramadol was recently approved by the Food and Drug Administration (FDA) in October 2021 for the treatment of acute pain in adults. OBJECTIVE: This paper presents the first published quantitative analytical methods for celecoxib and tramadol. METHODS: The UV absorption spectra of celecoxib and tramadol showed strong overlap. Mathematical simultaneous equation and ratio difference methods were developed to resolve the spectral overlap and quantify the drugs in the combination mixture. In the simultaneous equation method, the absorbance and absorptivity values at 252 and 217 nm were used to construct two mathematical equations that were used for the simultaneous mathematical quantification of the above drugs. The mathematical manipulation of the ratio difference based on the calculation of the differences in the amplitude values between 250 and 280 nm enabled the quantitative analysis of celecoxib, and the differences in the amplitude values between 221 and 272 nm enabled the quantitative analysis of tramadol. RESULTS: The proposed methods were successfully applied to the selective quantitative analysis of celecoxib and tramadol in the synthetic mixtures and in the pharmaceutical tablets without interference from the tablet additives. CONCLUSIONS: The applied methods demonstrated good linearity in the concentration range of 1-20 µg/mL and 3-45 µg/mL for celecoxib and tramadol, respectively, with acceptable accuracy and precision. The methods were found to be sensitive with LOD values of 0.183 µg/mL and 0.626 µg/mL for celecoxib and tramadol, respectively, in simultaneous equation method and of 0.275 µg/mL and 0.772 µg/mL for celecoxib and tramadol, respectively, in ratio difference method. HIGHLIGHTS: The first established simple and validated UV spectrophotometric methods were described for concurrent quantification of the celecoxib and tramadol in their recently approved pharmaceutical formulation.
Subject(s)
Analgesia , Tramadol , Adult , Analgesics, Opioid/therapeutic use , Celecoxib/therapeutic use , Humans , Pain/drug therapy , Pain Management , Tablets , Tramadol/therapeutic useABSTRACT
Two chromatographic techniques were developed and validated for simultaneous determination of the newly co-formulated antidiabetic combination linagliptin and empagliflozin in their pure form and film-coated tables. The first technique was UPLC; the separation and resolution of both analytes were achieved using a Zorbax eclipse plus C18 column applying an isocratic elution based on phosphate buffer pH 4-acetonitrile (65:35, v/v) as a running mobile phase at flow rate 1.5 ml/min and the effluent was monitored at 220 nm. Augmentation of Lean Six Sigma with UPLC and HPTLC methods had a major impact on the development of robust specifications to ensure that the quality at six sigma level has a high level of statistical confidence and target performance. On the chromatogram, empagliflozin and linagliptin appeared at retention times of 1.417 and 2.453 min, respectively. The second technique was HPTLC; both analytes were fairly well resolved and separated using a developing mobile phase composed of ethyl acetate-chloroform-acetonitrile (55:25:20 by volume). The values of retention factor (RF ) were 0.29 and 0.53 for linagliptin and empagliflozin, respectively. All variables were investigated to adjust the whole conditions.
Subject(s)
Benzhydryl Compounds/analysis , Chromatography, High Pressure Liquid/methods , Chromatography, Thin Layer/methods , Glucosides/analysis , Linagliptin/analysis , Limit of Detection , Linear Models , Reproducibility of Results , Tablets/chemistry , Total Quality ManagementABSTRACT
This is the first study focusing solely on that determination of tadalafil in the presence of citalopram as an antidepressant drug. The determination in biological fluids of a co-administered antidepressant drug and a sexual stimulation drug is a very critical and important step for psychotic and ischaemic heart disease patients, especially in cases of emergency and this requires therapeutic drug monitoring. A sensitive, efficient and rapid assay was selected satisfactorily and applied for simultaneous determination of citalopram and tadalafil either in their pure forms, in tablet dosage forms or in spiked human plasma. There was a large overlap for both drugs, forming the broad band found in conventional fluorescence spectra and their related synchronous fluorescence intensity. Therefore, the development of a highly sensitive second derivative synchronous fluorescence method was demonstrated that removed this overlap. The proposed method depended on measuring the amplitudes of the second derivative of synchronous fluorescence intensity at suitable wavelengths of 301 nm and 367 nm for citalopram and tadalafil at Δλ = 60 nm, respectively. Box-Behnken design as a response surface methodology was used to fit models and create an optimization process encompassing a set of factors and resulting in an optimum response value specifically designed for this method. Under optimum conditions, the linear dynamic ranges for citalopram and tadalafil estimation were 20-900 and 5-400 ng ml-1 with detection limits of 5.40 and 1.43 ng ml-1 , respectively.
Subject(s)
Citalopram , Humans , Spectrometry, Fluorescence , Staining and Labeling , Tablets , TadalafilABSTRACT
A new chemically optimized screen-printed electrode modified with a cobalt-doped α-Mn2O3 nanostructure on carbon nanotube paste (α-Mn2O3:Co@CNTs) has been constructed for the recognition of cyclobenzaprine hydrochloride. The prepared paste is based on the incorporation of oxide ion conductors, such as the α-Mn2O3 nanostructure with cobalt and ion pairs (tetraphenyl borate coupled with the drug), as electroactive species in the screen-printed electrode to increase the sensor surface area and decrease electrical resistance. The central composite design is a useful methodology for the estimation and modeling of the exact optimum parameters specifically designed for this process. This is a good way to graphically clarify the relationship between various experimental variables and the slope response. The proposed sensor, α-Mn2O3:Co@CNTs, possesses very good sensitivity and the ability to recognize the drug over the concentration range of 1 × 10-6 to 1 × 10-2 mol L-1 at 25 ± °C with a detection limit of 2.84 × 10-7 mol L-1. It exhibits a reproducible potential and stable linear response for six months at a Nernstian slope of 58.96 ± 0.76 mV per decade. The proposed electrode approach has been successfully applied in the direct determination of the drug in its pure and dosage forms.
ABSTRACT
Simultaneous determination of rosuvastatin calcium and propranolol hydrochloride using the first derivative synchronous spectrofluorimetry was described. This method involves measuring the synchronous fluorescence of both drugs in ethanol using, ∆ λâ¯=â¯60â¯nm then the first derivative was recorded and the peak amplitudes were measured at 350 and 374â¯nm for rosuvastatin calcium and propranolol hydrochloride, respectively. Under the optimum conditions, the linear ranges of rosuvastatin calcium and propranolol hydrochloride were 0.2-2⯵g/mL and 0.1-1⯵g/mL, respectively. The method was used for quantitative analysis of the drugs in raw materials and pharmaceutical dosage form. The validity of the proposed method was assessed according to an international conference on harmonization (ICH) guidelines.
Subject(s)
Propranolol/analysis , Rosuvastatin Calcium/analysis , Spectrometry, Fluorescence/methods , Buffers , Hydrogen-Ion Concentration , Limit of Detection , Reproducibility of Results , Solvents/chemistryABSTRACT
OBJECTIVE: The objective of this study was the evaluation of effects of locally administered zoledronic acid and alendronate on rate of osteogenesis in distracted mandible of dogs. STUDY DESIGN: Following mandibular corticotomy, bone segments were maintained in a neutral position by distractor for 7 days then distraction was initiated at a rate of 0.5 mm twice a day for 10 days to achieve a total distraction of 10 mm, followed by a consolidation period. Animals were divided into 3 equal groups according to the injected drug (saline solution [control], zoledronic acid, alendronate). The dogs were killed 2, 6, and 10 weeks following distraction and samples were collected for radiographic examination, assessment of bone mineral density, and histopathological evaluation. RESULTS: Radiographs and histopathological results pointed out that bone formation and maturation of experimental groups were faster than those of the control group. CONCLUSIONS: Local administration of zoledronic acid and alendronate proved to be effective in shortening the consolidation period.
Subject(s)
Alendronate/pharmacology , Diphosphonates/pharmacology , Imidazoles/pharmacology , Mandible/surgery , Osteogenesis, Distraction/methods , Osteogenesis/drug effects , Absorptiometry, Photon , Alendronate/administration & dosage , Animals , Bone Density , Diphosphonates/administration & dosage , Dogs , Imidazoles/administration & dosage , Mandible/diagnostic imaging , Osteotomy , Random Allocation , Zoledronic AcidABSTRACT
N-Protected-(aminoacyl)benzotriazoles 1a-e, g, i, j, 1a'-c' convert heterocyclic amines of the following series: thiazoles (3a and 3a'), benzothiazoles (3b and 3b'), benzimidazoles (3c and 3c'), thiadiazoles (3d), pyrimidones (9a, b, a'), pyrazoles (11a, b), and pyridines (13a-g, 13d') under microwave irradiation, into N-substituted amides in yields of 40-98% (average 76%). N-Protected peptidoylbenzotriazoles 6a, b similarly afforded C-terminal N-protected dipeptidoyl amides 7a, b (52-60%).
Subject(s)
Amines/chemistry , Heterocyclic Compounds/chemical synthesis , Aminoacylation , Benzene/chemistry , Heterocyclic Compounds/chemistry , Molecular Structure , Sulfhydryl Compounds/chemistryABSTRACT
[Structure: see text]. Reactions of readily available N-(alkyl-, aryl-, and heteroarylsulfonyl)benzotriazoles 3a-h with diverse nitriles, reactive heteroaromatics, alkylheteroaromatics, sulfones, and esters produced alpha-cyanoalkyl sulfones 5a-i, sulfonylheteroaromatics 7a-e, alpha-(sulfonylalkyl)heterocycles 9a-f, alpha-sulfonylalkyl sulfones 11a-g, and esters of alpha-sulfonyl acids 14a-c, respectively, in synthetically useful to excellent yields. The results represent the first examples of the successful application of sulfonylazoles for C-sulfonylation.
Subject(s)
Sulfones/chemistry , Sulfones/chemical synthesis , Sulfonic Acids/chemistry , Triazoles/chemistry , Triazoles/chemical synthesisABSTRACT
[Reaction: see text]. Readily available N-acylbenzotriazoles 2a-l (derived from a variety of aliphatic, (hetero)aromatic, and N-protected alpha-amino carboxylic acids) smoothly convert primary 3a-c and alpha-functionalized primary nitroalkanes 3d into the corresponding alpha-nitro ketones 5a-p in yields of 39-86% (average 63%).
ABSTRACT
[Chemical reaction: See text] Benzotriazole reagents for thioacylation (RCSBt), thiocarbamoylation (RR'NCSBt), aryl/alkoxythioacylation (ROCSBt), and aryl/alkylthiothioacylation (RSCSBt) are synthesized, and their utility is assessed by syntheses of representative heteroaryl thioureas 3a-g, thioamides 15a-s, thionoesters 16a-h, thiocarbamates 17a-e, dithiocarbamates 18a-d, thiocarbonates 19a-c, and dithiocarbonates 20a-c.
ABSTRACT
Nucleophilic addition of alkyl- and benzylthiols to benzoquinone diimine (1) gave the corresponding 3-alkylthio- or 3-benzylthio-1,4-phenylenediamines (2-5). However, addition of aryl- or heteroarylthiols to 1 formed 2-arylthio- or 2-heteroarylthio-1,4-phenylenediamines (6-14). The structures of 2-14, obtained in 55-91% yields, were confirmed in CDCl3 or DMSO-d6 solution using 1D (NOE difference, coupled 13C NMR spectra, APT and DEPT) and 2D NMR techniques [DQCOSY, NOESY, HETCOR and heteronuclear multiple bond coherence (HMBC)] that resulted in unambiguous proton and carbon NMR resonance assignments. The substituent-induced 13C NMR chemical shift differences were calculated in 2-14 relative to carbon atoms in the model compound N1-(1,3-dimethylbutyl)-N4-phenyl-1,4-phenylenediamine (DMBPPD) (15) (a reduced form of benzoquinone diimine).
Subject(s)
Hydrocarbons, Aromatic/analysis , Hydrocarbons, Aromatic/chemistry , Magnetic Resonance Spectroscopy/methods , Models, Molecular , Phenylenediamines/analysis , Phenylenediamines/chemistry , Carbon Isotopes , Molecular Conformation , Phenylenediamines/classificationABSTRACT
Primary and secondary cyanides are efficiently acylated with N-acylbenzotriazoles 3a-f (derived from a variety of acids) to afford the corresponding alpha-substituted beta-ketonitriles 5a-r in 67-96% yields.
ABSTRACT
Acyclic sulfones 4a-f and alicyclic sulfone 7 react with readily available N-acylbenzotriazoles 3a-g (derived from aliphatic, aromatic, and heteroaromatic carboxylic acids) to provide the corresponding beta-keto sulfones 5a-n and 8a-c, respectively, in good to excellent yields.
ABSTRACT
OBJECTIVE: To determine the functionality of identified polymorphisms in the promoter and upstream regions of the interleukin-10 gene in terms of release of interleukin-10 from lipopolysaccharide-stimulated whole blood from healthy volunteers and to evaluate the relationship of interleukin-10 polymorphisms to interleukin-10 release, development of sepsis, and mortality in critically ill patients. DESIGN: Observational study. SETTING: The academic unit of anesthesia and intensive care, university laboratories, and ten-bed general intensive care unit in a university teaching hospital. SUBJECTS: A total of 132 healthy volunteers plus 67 consecutive critically ill patients recruited within 24 hrs of admission to the intensive care unit, regardless of diagnosis. MEASUREMENTS: Plasma interleukin-10 levels were measured by enzyme-linked immunosorbent assay. Single nucleotide polymorphisms were detected by restriction fragment length polymorphism analysis. Dinucleotide repeat polymorphisms were identified after polymerase chain reaction using a DNA size analyzer. MAIN RESULTS: Stimulated interleukin-10 release in critically ill patients was significantly lower than in healthy subjects (p < .0001). In addition, in the patients who developed sepsis, interleukin-10 release at admission to the intensive care unit was significantly lower than in patients who did not subsequently develop sepsis (median [range] 1.47 [0.13-6.90] ng/mL compared with 4.93 [0.03-16.80] ng/mL, p = .001). The A allele of the single nucleotide polymorphism at -592 base pairs was associated with lower interleukin-10 release and higher mortality in critically ill patients. Other polymorphisms were not linked to interleukin-10 release, sepsis, or mortality. CONCLUSIONS: The A allele of the -592 base pair single nucleotide polymorphism in the interleukin-10 gene is associated with lower stimulated interleukin-10 release and increased mortality. Further investigations are required to determine the nature of the functionality and the potential diagnostic and therapeutic aspects of this marker.
Subject(s)
Critical Illness/mortality , Genetic Markers/genetics , Interleukin-10/genetics , Polymorphism, Single Nucleotide , Sepsis/genetics , Sepsis/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Interleukin-10/blood , Male , Microsatellite Repeats , Middle Aged , Statistics, Nonparametric , Survival Rate , United Kingdom/epidemiologyABSTRACT
Reactions of organometallic reagents with 1-(substituted ethynyl)-1H-1,2,3-benzotriazoles 5 derived from a variety of benzotriazolylmethyl ketones 3 afforded disubstituted acetylenes in synthetically useful yields.