Investigating matrix interference in the pharmacopeial limit test for aluminum in citric acid: a re-examination, for revision of the method

In many pharmacopoeias, the limit test used for determining the level of aluminum in citric acid labeled for use in the manufacture of dialysate, is based on solvent extraction using 8-hydroxyquinoline and measurement of fluorescence. However, the fluorescence intensity (F.I.) readout from the extract of citric acid samples has been found to be highly dubious, showing low value, and even lower than that of a blank solution. The aim of this work therefore was to examine what effects the matrix has on the test. The comparison of the two standard curves of aluminum solutions in water, against those prepared in citric acid solutions revealed that they differed greatly in terms of slope and y-intercept. In addition, the F.I. values on the plot of the citric acid solution were much lower than that prepared in the water. In another experiment, a decrease in the F.I. of aluminum solution was clearly seen when the co-existing concentration of citric acid was increased. The results inferred that citric acid interfered with the test due to its acidity and metal-chelating capabilities. Based on this evidence, the pharmacopeial limit test for aluminum in citric acid should be revised; otherwise, it could yield results that underestimate aluminum levels and lead to inaccurate conclusions

Corrosion Inhibition Properties of Thiazolidinedione Derivatives for Copper in 3.5 wt.% NaCl Medium

Copper is the third-most-produced metal globally due to its exceptional mechanical and thermal properties, among others. However, it suffers serious dissolution issues when exposed to corrosive mediums. Herein, two thiazolidinedione derivatives, namely, (Z)-5-(4-methylbenzylidene)thiazolidine-2,4-dione (MTZD) and (Z)-3-allyl-5-(4-methylbenzylidene)thiazolidine-2,4-dione (ATZD), were synthesized and applied for corrosion protection of copper in 3.5 wt.% NaCl medium. The corrosion inhibition performance of tested compounds was evaluated at different experimental conditions using electrochemical impedance spectroscopy (EIS), potentiodynamic polarization curves (PPC) and atomic force microscopy (AFM). EIS results revealed that the addition of studied inhibitors limited the dissolution of copper in NaCl solution, leading to a high polarization resistance compared with the blank solution. In addition, PPC suggested that tested compounds had a mixed-type effect, decreasing anodic and cathodic corrosion reactions. Moreover, surface characterization by AFM indicated a significant decrease in surface roughness of copper after the addition of inhibitors. Outcomes from the present study suggest that ATZD (IE% = 96%) outperforms MTZD (IE% = 90%) slightly, due to the presence of additional –C3H5 unit (–CH2–CH = CH2) in the molecular scaffold of MTZD.

The magnetic stir bar as a source of impurities in laboratory blank solutions of the environmental samples subjected to microwave-assisted acid digestion

Teflon-coated magnetic stir bars are suspected to be a source of impurities for the laboratory blank solutions. To evaluate the ability of magnetic bars to absorb and release different elements at sub-ppb and above-ppb (µg L-1) level the experiment with new and used bars was conducted. The bars were subjected to microwave-assisted acid digestion with the soil sample and a series of successive cleaning procedures. The ICP-OES/MS analysis of the obtained extracts revealed that most of the elements may be released during subsequent extractions in the ppb-level concentrations, whereas the following elements: Cr, Cu, Sb, Sn, and Pb may be extracted even in elevated concentrations. SEM/EDS inspection of Teflon surfaces demonstrated the multiple defects that probably increase the absorption of the elements. We concluded that the concentration of mineral impurities in the laboratory blank solution prepared in the randomly selected one vessel per sample preparation batch is hardly propagated to the other used vessels. The alternative concept "blank per vessel" was proposed especially for ultra-trace analysis. Also, an additional step in the bar washing procedure was proposed.

Innovative Method Development Comprehensive Separation of Impurities and Validation for a novel Antipsychotic Drug Blonanserin

Blonanserin an antipsychotic novel drug used for the treatment of schizophrenia has antagonist properties for dopamine D2 and serotonin 5-HT2. On the other hand, it lacks adrenergic-α1, muscarinic M1, and histamine H1 antagonist activities. Clinical studies demonstrated in Japan had shown to be more effective for treating negative as well as positive schizophrenic symptoms. This drug was accepted and approved worldwide in the treatment of schizophrenia. A new HPLC method was developed and validated for the estimation of Impurities of Blonanserin (BNS) to ensure that the methodology meets the requirements of the target analysis application. Active and efficient chromatographic separation was achieved on a Zorbax Bonus RP EP C18 column having a particle size of 5μm, with dimensions of 250mm × 4.6 mm, mobile phase containing pH 2.4 buffer and Organic, with 1.0 ml /min flow rate, column oven temperature at 30oC and the eluent detection at 245 nm. The method shows well-separated impurities, is specific without interference from blank solution with resolution more than 1.2 between any of the impurity, correlation coefficient more than 0.99 showing good linearity; mean recovery ranging from 97% to 105% and is very sensitive at lower detection and quantification limits. This method was well developed and has been applied successfully to monitor and estimate impurities in Blonanserin.

Development and Validation of a Method for the Semi-Quantitative Determination of N-Nitrosamines in Active Pharmaceutical Ingredient Enalapril Maleate by Means of Derivatisation and Detection by HPLC with Fluorimetric Detector

A novel HPLC method with fluorimetric detection was developed for the determination of potentially carcinogenic N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) in active pharmaceutical ingredient enalapril maleate. N-nitrosamines were subject to denitrosation followed by derivatisation with dansyl chloride or fluorenylmethoxycarbonyl chloride (Fmoc-Cl). Fmoc-Cl offers much better sensitivity and repeatability than dansyl chloride derivatisation. A satisfactory linearity was obtained for the method, with R2 = 0.9994 for NDMA and 0.9990 for NDEA, and a limit of quantification level of 0.038 μg/g for NDMA and 0.050 μg/g for NDEA. The precision decreased with the concentration to a maximum level of about 10%. The recoveries were in the range of 74.2 ± 4.2% to 101.6 ± 16.1% for NDMA and 90.6 ± 2.9% to 125.4 ± 7.4% for NDEA. Dansyl chloride was found to be an inappropriate derivatisation agent, mainly due to potential contamination with dimethylamine, leading to unrepeatable peaks in the blank solution. Since the method involves the derivatisation of amines liberated from the N-nitrosamines, it was necessary to remove the amines from the test sample. Several critical points in the standard/sample preparation have been mentioned, which affect the reproducibility of the method and are not covered in similar articles.

Evaluation of Direct and Indirect Antioxidant Properties of Selected Four Natural Chemical Compounds: Quercetin, Epigallocatechin-3-Gallate, Indole-3-Carbinol and Sulforaphane by DPPH Radical Scavenging Assay

The main characteristic of antioxidants is the capacity to scavenge free radicals produced during cell metabolism, and thus they prevent oxidative stress, which may reduce the risk of many diseases. In this study, we evaluate the antioxidant properties of selected four compounds Quercetin (Q), Epigallocatechin-3-Gallate, (EGCG), Indole-3-Carbinol (I3C) and Sulforaphane (SF) by DPPH assay. The view is to establish the distinction between direct and indirect antioxidants, which would be the form of the basis for subsequent cellular antioxidant assays in our further studies. For sample assay: 20 μL of antioxidant solutions of Q, EGCG, I3C, and SF was added to 180 of 2,2- Diphenyl-1-Picrylhydrazyl (DPPH) solution. For blank solution, DMSO was used. Leaving the plate for 15 min in a dark place and measure the absorbance at 540 nm. The results demonstrated that Q and EGCG possess direct antioxidant properties, which can be used in further cellular studies. I3C and SFN did not appear to possess any direct antioxidant behaviours during DPPH radical scavenging.

Folic acid affects cardiometabolic, oxidative stress, and immunohistochemical parameters in monocrotaline-induced rat heart failure

Heart failure (HF) is one of the major cardiovascular causes of death worldwide. In this study, we explored the effects of folic acid (FA) on cardiometabolic, oxidative stress biomarker changes, and the activity of proliferation marker Ki67 in monocrotaline-induced HF. The research was conducted during a 4 week period using five experimental groups (eight animals per group): blank solution exposed controls (C1: 1 mL/kg physiological saline, 1 day; C2: 1 mL/kg physiological saline, 28 days), monocrotaline (MCT) induced HF (50 mg/kg MCT), FA (5 mg·kg−1·day−1 FA), and MCT+FA (50 mg/kg MCT, 5 mg·kg−1·day−1 FA). Superoxide dismutase and glutathione peroxidase activities together with total glutathione and parameters of oxidative damage of proteins were determined in cardiac tissue as well as cardiometabolic parameters in plasma or serum. The total glutathionylation was determined by Western blot and proliferation marker Ki67 was assessed by immunohistochemistry. The right ventricular (RV) wall hypertrophy and Ki67 positivity, accompanied by a significant increase of troponin T, has been shown in MCT-induced HF. The antioxidant effect of FA was reflected through superoxide dismutase activity, reduced Ki67 positivity in the RV wall, and a slightly decreased total glutathionylation level.

Potensi Ekstrak Buah Buni (Antidesma bunius (L) Spreng) Sebagai Inhibitor Enzim α-Glukosidase

Diabetes mellitus is still a global health problem that continues to increase rapidly and become one of the major metabolic diseases throughout the world. This study aims to determine the potential of Buni fruit as an α-glucosidase inhibitor. α-glucosidase inhibition test is carried out on a blank solution (test solution without sample/standard), acarbose solution as a comparison standard and samples are carried out in accordance with the optimization conditions obtained. The rendemen percent of green and red buni fruit extract yields are 6.35% and 3.09%, respectively. The results of the identification of secondary metabolites using TLC showed that green and red buni fruit extract contains flavonoid, phenolic and alkaloid compounds. The results of the α-glucosidase enzyme inhibition test showed that the red buni fruit extract had the highest activity compared to green buni fruit extract with an IC50 value of 85.27 ppm.

Aktivitas hidrolisat protein terhadap perkecambahan dan pertumbuhan awal kacang hijau (Vigna radiata)

Plant bostimulant application have proven to improve field productivity to meet genetic potential. Protein hydrolisates has been utilized as plant biostimulant to increase crops productiviy and yield. Protein hydrolysate from organic waste or by product is highly potential for plant biostimulant, since it is efficiently turn the waste into high value product.. Trash fish meal (TI) and chicken feather meal (TB) have high protein content and are potential as plant biostimulant. Application of protein hydrolisates as biostimulant has been acclaimed to improve plant growth. The aim of this study wasto evaluate the activity of protein hydrolysates from TB and TI on germination and early growth of mung bean. Hydrolysis was conducted under high temperature and pressure in acid condition. Application of protein hydrolysates under various concentrations: 5, 10, and 20 ppm. The effect of protein hydrolysates were evaluated on seed germination and root and colleoptile fresh weight. Chemical analysis was performed to measure nitrogen content in the materials. The result showed that germination at 10 ppm after 7 hours incubation of protein hydrolysate from TI and TB. Under TI hydrolysate germination was increase by 191.7%, from 21.7% blank solution to 63.3% of treatment. While under protein hydrolysate from TB increased by 99.5%, from 21.7% of blank solution to 43.3%. Activity of TB hydrolysate toward root and colleoptile growth was higher than in TI hydrolysate. Root growth was higher than colleoptile under all treatments. Protein hydrolysates of TI and TB could improve germination and early growth of mung bean and is highly potential as plant biostimulant.[Keywords: plant biostimulant, protein hydrolysis, plant growth, Vigna radiata]AbstrakAplikasi biostimulan tanaman terbukti mampu meningkatkan produktivitas riil di lapang sehingga mendekati potensi genetik tanaman. Hidrolisat protein telah dimanfaatkan sebagai biostimulan tanaman untuk meningkatkan produktivitas dan hasil panen berbagai tanaman. Hidrolisat protein dari limbah atau produk samping sangat potensial dikembangkan sebagai biostimulan tanaman karena mampu secara efisien mengubah sampah menjadi produk berharga. Tepung ikan rucah (TI) dan tepung bulu ayam (TB) adalah produk samping usaha perikanan dan peternakan dengan kandungan protein tinggi yang sangat potensial dikembangkan menjadi biostimulan untuk meningkatkan pertumbuhan tanaman. Tujuan penelitian ini adalah untuk mengetahui aktivitas hidrolisat protein dari TI dan TB terhadap perkecambahan dan pertumbuhan awal kacang hijau. Hidrolisis dilakukan pada suhu dan tekanan tinggi dalam kondisi asam. Hidrolisat yang diperoleh selanjutnya diaplikasikan pada benih kacang hijau pada konsentrasi 5, 10, dan 20 ppm. Parameter yang diamati berupa persentase perkecambahan dan pertumbuhan akar dan koleoptil semai. Analisis kimia dilakukan untuk memberikan data pendukung berupa kadar nitrogen pada kedua bahan baku. Hasil penelitian menunjukkan terjadinya peningkatan aktivitas perkecambahan kacang hijau pada inkubasi selama 7 jam dalam larutan 10 ppm hidrolisat TI dan TB. Kenaikan persentase perkecambahan pada hidrolisat TI sebesar 191,7%, yaitu dari 21,7% pada blanko menjadi 63,3% pada perlakuan. Sementara dalamhidrolisatTBpeningkatan aktivitas mencapai 99,5%, yaitu dari 21,7% pada blankomenjadi 43,3% pada perlakuan. Pertumbuhan akar dan koleoptil dengan aplikasi hidrolisat TB lebih tinggi dibandingkan pada aplikasi hidrolisat TI. Pengaruh hidrolisat protein lebih tinggi pada pertumbuhan akar dibandingkan koleoptil. Hidrolisat TI dan TB mampu meningkatkan perkecambahan dan pertumbuhan awal kacang hijau dan sangat potensial dikembangkan sebagai biostimulan tanaman. [Kata kunci:biostimulan tanaman, hidrolisisprotein, pertumbuhan tanaman,Vigna radiata]

Spectrophotometric determination of niclosamide Via Schiff ’s base formulations in pharmaceutical and veterinary preparations

Introduction: Niclosamide(NICS) its chemical name 5-chloro-N-(2- chloro-4-nitrophenyl)-2-hydroxybenz-amide]is the only commercially existing molluscicide optional by the WHO for large extent use in schistosomiasis be in charge of programs . NICS and its two new synthesized derivatives constructed to float on the water surface were able to kill cercariae, also obsessed promising activity in vitro nearby to an apicomplexan parasite Toxoplasma (4). Few spectrophotometric methods have been reported for the estimation of NICS as pure and in formulations, approximately these methods depend on reduction of nitro group (almost with zinc powder in acidic medium) followed by reaction with different reagents. The method based on reduction of nitro group of NICS then reaction of reduced-NICS with para- N,N dimethylaminobenzaldehyde in non-aqueous medium (methanol) to form a colored product that has been proved successfully for the estimation of NICS in pharmaceutical and veterinary formulations Material and method :All reagents used are of analytical grade and are obtained from Fluka or Aldrich , NICS wassupplied from SIGMA companies. Methanolic solution of para- N,N- dimethylanimobenzaldehyde (Fluka)3%, weighing 3 g and dissolved in 100 ml methanol in a volumetric flask. All other reagents were prepared bydissolving the propriety weight in perfect solvent. A volume in the range of 0.1 to 1.7 ml of 100 µg.ml-1RNICS solution was transferred to 10 ml calibrated flasks.2ml of PNNDMABA (3.0 %) was added, and the volume was made up to 10 ml by adding methanol. The yellow Schiff ’s base was measured at 454 nm versus a blank solution. Results and Discussion:The optimum pH for reaction of NICS with para-N, N-dimethylanimobenzaldehyde equal to 3 which resulted by mixing the components of the reaction. The absorbance increase with increasing reagent concentration (para-N,N- dimethylanimobenzaldehyde) and reached maximum on adding volume of 2.0 ml of (3%), which also gives the highest value of determination coefficient (R2).The experimental data indicated that methanol was the optimum solvent used in dilution according to high intensity of Schiff ’s base and the good stability. The formation of the yellow Schiff ’s base being complete after mixing the components of reaction and the absorbance remained constant for at least 2 hours. Conclusion: Accurate and sensitive spectrophotometric method was described for the estimation of NICS. The present method has been successfully applied for the estimation of NICS in pharmaceutical and veterinary preparations.