46 research outputs found
Purity assessment and determination of sertaconazole in bulk and pharmaceutical formulations based on spectrophotometric and chromatographic approaches
Stability evaluation of the drug substance is an integral part of the systematic approach to stability studies. Hence, three simple, sensitive and precise methods depending on two different techniques as UV spectrophotometry and chromatography were adopted for the task of stability indicating determination of sertaconazole (SER) in presence of its acidic degradation products. The first method is Zero-crossing first derivative (1D) spectrophotometric one, which allows the determination of SER over a concentration range of 4-64 ”g/mL at 290 nm with mean percentage recoveries 99.77±0.781. While first-derivative of the ratio spectra (1DR) is the method of choice for determination of pure SER at a maximum 300 nm and at a trough 304 nm, with mean percentage recoveries 99.98±0.720 and 100.46±0.640, respectively. The third developed HPLC method used a RP-ZORBAX C18 column (5 ÎŒm particle size, 250Ă4.6 mm; id) with isocratic elution. The mobile phase was methanol: 0.2% formic acid aqueous solution (75:25, v:v); pH = 3.5 at the flow rate of 1.0 mL/min, with UV detection at 260 nm. The method could determine SER in the range of 0.8-40 ”g/mL with a mean percentage recovery of 99.65±0.630. The developed methods were succeeded in the determination of SER in bulk powder, pharmaceutical dosage forms and in presence of its acidic degradation products. The results obtained were validated in compliance with ICH guidelines and compared statistically with each other and to those of the official method in the British Pharmacopoeia regarding both accuracy and precision
Stability-indicating methods for the determination of olanzapine in presence of its degradation products
Simple, sensitive and precise spectrophotometric and chemometric stability indicating techniques were adopted for Olanzapine (OLA) determination in presence of its degradation products over a concentration range of 0.002-0.02 mg/mL. The spectrophotometric technique involves six methods; first method is first derivative (D1) spectrophotometric one, which allows the determination of OLA in presence of its acidic and alkaline degradation products at 261.2 and 260.6 nm with mean percentage recoveries of 99.90±0.48 and 99.95±0.67, respectively. While second derivative spectrophotometry (D2) was used for determination of drug in presence of alkaline degradation products. Second method is first-derivative of the ratio spectra (DR1) for determination of OLA in presence of its acidic and alkaline degradation products at 267.9 and 251.6 nm, respectively with mean percentage recoveries of 99.81±0.64 and 100.53±1.11, respectively. The third method is pH-induced difference method for determination of OLA in presence of its acidic and alkaline degradation products; with mean percentage recoveries 100.09±0.06 and 99.77±0.78, respectively. Fourth method is the Q-analysis (absorption ratio) method, which involves the formation of absorbance equation at 296.3 nm (isosbestic point) and 271 nm (λmax of OLA) for the determination of OLA in presence of its acidic degradation products. The mean percentage recovery is 100.07±1.51. Fifth method based on dual wavelength selection was developed for the determination of OLA in presence of its acidic degradation products with mean percentage recovery of 100.36±0.69. Sixth method based on simple mathematic algorithm by the bivariate calibration was also used for the determination of OLA with the mean percentage recovery of 101.72±1.10. The second technique is chemometrics, which includes determination of OLA in presence of its acidic degradation products using multivariate calibration methods (the classical least squares (CLS), principle component regression (PCR) and partial least squares (PLS)) using the information contained in the absorption spectra
Genotype, age, genetic background, and sex influence Epha2-related cataract development in mice
Purpose: Age-related cataract is the leading cause of blindness worldwide. Variants in the EPHA2 gene increase the disease risk, and its knockout in mice causes cataract. We investigated whether age, sex, and genetic background, risk factors for age-related cataract, and Epha2 genotype influence Epha2-related cataract development in mice. Methods: Cataract development was monitored in Epha2+/+, Epha2+/â, and Epha2â/â mice (Epha2Gt(KST085)Byg) on C57BL/6J and FVB:C57BL/6J (50:50) backgrounds. Cellular architecture of lenses, endoplasmic reticulum (ER) stress, and redox state were determined using histological, molecular, and analytical techniques. Results: Epha2â/â and Epha2+/â mice on C57BL/6J background developed severe cortical cataracts by 18 and 38 weeks of age, respectively, compared to development of similar cataract significantly later in Epha2â/â mice and no cataract in Epha2+/â mice in this strain on FVB background, which was previously reported. On FVB:C57BL/6J background, Epha2â/â mice developed severe cortical cataract by 38 weeks and Epha2+/â mice exhibited mild cortical cataract up to 64 weeks of age. Progression of cataract in Epha2â/â and Epha2+/â female mice on C57BL/6J and mixed background, respectively, was slower than in matched male mice. N-cadherin and ÎČ-catenin immunolabeling showed disorganized lens fiber cells and disruption of lens architecture in Epha2â/â and Epha2+/â lenses, coinciding with development of severe cataracts. EPHA2 immunolabeling showed intracellular accumulation of the mutant EPHA2-ÎČ-galactosidase fusion protein that induced a cytoprotective ER stress response and in Epha2+/â lenses was also accompanied by glutathione redox imbalance. Conclusions: Both, Epha2â/â and Epha2+/â mice develop age-related cortical cataract; age as a function of Epha2 genotype, sex, and genetic background influence Epha2-related cataractogenesis in mice
Low intrinsic efficacy for G protein activation can explain the improved side-effect profile of new opioid agonists
Biased agonism at G proteinâcoupled receptors describes the phenomenon whereby some drugs can activate some downstream signaling activities to the relative exclusion of others. Descriptions of biased agonism focusing on the differential engagement of G proteins versus ÎČ-arrestins are commonly limited by the small response windows obtained in pathways that are not amplified or are less effectively coupled to receptor engagement, such as ÎČ-arrestin recruitment. At the ÎŒ-opioid receptor (MOR), G proteinâbiased ligands have been proposed to induce less constipation and respiratory depressant side effects than opioids commonly used to treat pain. However, it is unclear whether these improved safety profiles are due to a reduction in ÎČ-arrestinâmediated signaling or, alternatively, to their low intrinsic efficacy in all signaling pathways. Here, we systematically evaluated the most recent and promising MOR-biased ligands and assessed their pharmacological profile against existing opioid analgesics in assays not confounded by limited signal windows. We found that oliceridine, PZM21, and SR-17018 had low intrinsic efficacy. We also demonstrated a strong correlation between measures of efficacy for receptor activation, G protein coupling, and ÎČ-arrestin recruitment for all tested ligands. By measuring the antinociceptive and respiratory depressant effects of these ligands, we showed that the low intrinsic efficacy of opioid ligands can explain an improved side effect profile. Our results suggest a possible alternative mechanism underlying the improved therapeutic windows described for new opioid ligands, which should be taken into account for future descriptions of ligand action at this important therapeutic target
Cross-linking of a biopolymer-peptide co-assembling system
ProducciĂłn CientĂficaThe ability to guide molecular self-assembly at the nanoscale into complex macroscopic structures could enable the development of functional synthetic materials that exhibit properties of natural tissues such as hierarchy, adaptability, and self-healing. However, the stability and structural integrity of these kinds of materials remains a challenge for many practical applications. We have recently developed a dynamic biopolymer-peptide co-assembly system with the capacity to grow and undergo morphogenesis into complex shapes. Here we explored the potential of different synthetic (succinimidyl carboxymethyl ester, poly (ethylene glycol) ether tetrasuccinimidyl glutarate and glutaraldehyde) and natural (genipin) cross-linking agents to stabilize membranes made from these biopolymer-peptide co-assemblies. We investigated the cross-linking efficiency, resistance to enzymatic degradation, and mechanical properties of the different cross-linked membranes. We also compared their biocompatibility by assessing the metabolic activity and morphology of adipose-derived stem cells (ADSC) cultured on the different membranes. While all cross-linkers successfully stabilized the system under physiological conditions, membranes cross-linked with genipin exhibited better resistance in physiological environments, improved stability under enzymatic degradation, and a higher degree of in vitro cytocompatibility compared to the other cross-linking agents. The results demonstrated that genipin is an attractive candidate to provide functional structural stability to complex self-assembling structures for potential tissue engineering or in vitro model applications.Ministerio de EconomĂa, Industria y Competitividad (Project MAT2013-42473-R and MAT2015-68901R)Junta de Castilla y LeĂłn (programa de apoyo a proyectos de investigaciĂłn â Ref. VA244U13, VA313U14 and VA015U
Derivative UV/Vis spectroelectrochemistry in a thin-layer regime: deconvolution and simultaneous quantification of ascorbic acid, dopamine and uric acid
In this work, UV/Vis spectroelectrochemistry (SEC), in a thin-layer regime and parallel configuration, is selected to solve a
complex mixture that contains dopamine (DA), ascorbic acid (AA) and uric acid (UA). These molecules, like many other
biological compounds, are assuming a highly important place in analytical and biomedical fields due to the fundamental role
that they play in human metabolism. In addition, low or high levels of these compounds are associated with diseases such as
Parkinsonâs disease. For this reason, the quantification of these biomolecules is becoming increasingly critical. However, some
drawbacks must be overcome, because the three molecules coexist in the human body, and the species are subject to mutual
interference. In fact, they are all oxidized at similar potentials, and their UV/Vis absorption bands overlap, greatly complicating
their quantification. For this reason, derivative SEC together with suitable chemometric tools such as PARAFAC are proposed to
solve this complex matrix. This technique allows us to separate the contribution of each of these molecules present in a sample
and to quantify all of them, achieving high resolution and reproducibility. Besides, detection limits at the micromolar level are
achieved for DA, AA and UA in mixture solutions. This work thus demonstrates the great potential for derivative potentiodynamic
SEC combined with the appropriate chemometric tools in solving complex mixtures, a field where SEC is still taking the
first steps.Ministerio de EconomĂa y Competitividad (Grants CTQ2017-83935-RAEI/
FEDER, UE), Junta de Castilla y LeĂłn (Grant BU297P18) and
Ministerio de Ciencia, InnovaciĂłn y Universidades (RED2018-102412-
T). F.O. is grateful for the contract funded by Junta de Castilla y LeĂłn, the
European Social Fund and the Youth Employment Initiative. J.G.R.
thanks theMinisterio de EconomĂa y Competitividad for his postdoctoral
contract (CTQ2017-83935-R AEI/FEDER, UE)
Te haÌ o te whaÌnau : how MaÌori social service practitioners support whaÌnau affected by whaÌnau violence : Te haÌ o te whaÌnau : how MaÌori social service practitioners support whaÌnau affected by whaÌnau violence
There is a dearth of knowledge regarding violence and MÄori whÄnau written from the perspectives of MÄori women, social service practitioners and other professionals, however, the literature comes from a national perspective. Literature from a local perspective is sparse on how MÄori whÄnau affected by whÄnau violence are supported. This research explores the perspectives of four MÄori social service practitioners on how they support whÄnau affected by whÄnau violence in the Eastern Bay of Plenty region. This research focuses on the exploration of a whole of whÄnau approach to whÄnau violence. It is not aimed at individuals. Rather, it is recognised that each person is a part of a collective and in terms of whÄnau violence, collective healing needs to occur. Consulting MÄori social service practitioners about effective interventions and barriers to effective interventions may contribute to more beneficial outcomes for whÄnau, now and into the future so mokopuna grow up in violence-free homes. This research project draws on a kaupapa MÄori qualitative methodology and a semi structured focus group interview was conducted with four MÄori social service practitioners. The results of the research are consistent with the reviewed literature regarding the effects of colonisation on MÄori, however, some new perspectives were offered regarding supporting whÄnau in rural communities. Government policy, decisions and funding that impacted on MÄori social service practitionerâs ability to support whÄnau is of considerable concern. The formulation, design and implementation of kaupapa MÄori interventions in the Eastern Bay of Plenty would be a step in a positive direction in order to effectively support whÄnau
Validated stability-indicating methods for the determination of zafirlukast in the presence of its alkaline hydrolysis degradation product
Three simple stability-indicating methods for the analysis of Zafirlukast (ZAF) in the presence of its alkaline degradation products were developed and validated as per the International Conference on Harmonization (ICH) guidelines to evaluate the stability-indicating power of the proposed methods. The developed high-performance liquid chromatographic technique was achieved on ZORBAXâODS (5 Όm, 150 Ă 4.6 mm, i.d.) by isocratic elution with a mixture of acetonitrile/0.05 M phosphate buffer, pH 5.0, (50:50; v/v) as a mobile phase at flow rate of 1.0 mL minâ1, followed by UV detection at 240 nm. The method could determine ZAF in the range of 2â40 Όg mLâ1 with a mean percentage recovery of 99.73 ± 0.903. The proposed HPLC method was utilized to investigate the kinetics of alkaline degradation of ZAF. First derivative of the ratio spectra (1DD) method was applied to analyze the drug under investigation without any interference from its degradation product with a linearity range of 4â32 Όg mLâ1 and with a mean percentage recovery of 99.85 ± 0.608. A chemometric method was also developed using the partial least squares (PLS) model for selective determination of ZAF in the range of 4â40 Όg mLâ1, the mean percentage recovery was found to be 100.00 ± 0.336
Purity assessment and determination of sertaconazole in bulk and pharmaceutical formulations based on spectrophotometric and chromatographic approaches
Stability evaluation of the drug substance is an integral part of the systematic approach to stability studies. Hence, three simple, sensitive and precise methods depending on two different techniques as UV spectrophotometry and chromatography were adopted for the task of stability indicating determination of sertaconazole (SER) in presence of its acidic degradation products. The first method is Zero-crossing first derivative (1D) spectrophotometric one, which allows the determination of SER over a concentration range of 4-64 ”g/mL at 290 nm with mean percentage recoveries 99.77±0.781. While first-derivative of the ratio spectra (1DR) is the method of choice for determination of pure SER at a maximum 300 nm and at a trough 304 nm, with mean percentage recoveries 99.98±0.720 and 100.46±0.640, respectively. The third developed HPLC method used a RP-ZORBAX C18 column (5 ÎŒm particle size, 250Ă4.6 mm; id) with isocratic elution. The mobile phase was methanol: 0.2% formic acid aqueous solution (75:25, v:v); pH = 3.5 at the flow rate of 1.0 mL/min, with UV detection at 260 nm. The method could determine SER in the range of 0.8-40 ”g/mL with a mean percentage recovery of 99.65±0.630. The developed methods were succeeded in the determination of SER in bulk powder, pharmaceutical dosage forms and in presence of its acidic degradation products. The results obtained were validated in compliance with ICH guidelines and compared statistically with each other and to those of the official method in the British Pharmacopoeia regarding both accuracy and precision