Potassium Dihydrogen Phosphate Solution Research Articles

Effect of Various Sizes of Calcined Marsh Clam Shell on Phosphate Removal from Aqueous Solution

Phosphorus is one of essential elements for sustaining life largely through phosphate, a compound containing the phosphate ion, PO43−. However, excessive phosphorus concentrations will cause eutrophication and this condition is considered as an environmental issue. The phosphorus sources are commonly from human activities; for instance, detergents, fertilisers, and industries. Although various adsorption techniques have been applied to remove phosphorus in water, the effect of different particle sizes of calcined marsh clam shells on phosphate removal has not been fully investigated, along with its adsorption kinetics and isotherms. This study investigates phosphate removal from synthetic solution onto calcined marsh clam shells (CMCs) with 5 different particle sizes: 0.075–0.15, 0.15–0.30, 0.30–0.60, 0.60–1.18, and 1.18–2.36 mm. The batch experiment used 2 g of adsorbent and synthetic potassium dihydrogen phosphate (KH2PO4) solution. The adsorbent size of 0.075 to 0.15 mm showed the highest removal (100%) efficiency due to high adsorption rate. The experimental data were further analysed using kinetics and isotherm models; the data fitted well with pseudo-second-order kinetic model (R2 = 0.9986) and Freundlich isotherm model (R2 = 0.8404). The potential of marsh clam shells as an adsorbent for phosphate removal in water is significant for future applications in wastewater treatment technology.

Reverse‐phase high‐performance liquid chromatography methodology for film‐forming mafenide spray: Compatibility, assay, and in‐vitro release evaluation using Franz vertical diffusion cell apparatus

AbstractThis paper described a short and precise reverse‐phase high‐performance liquid chromatography (HPLC) method for quantifying mafenide in a film‐forming spray and preliminary in‐vitro release study. Following the International Council for Harmonization guidelines Q2 (R1), the method was validated. The chromatographic separation was achieved using a 10 mM potassium dihydrogen phosphate solution (mobile phase A) mixed with HPLC‐grade methanol (mobile phase B) in an 85:15 v/v ratio. Inert Sustain C8 (4.6 × 250 mm), 5 μm column was selected as the stationary phase. The flow rate was set as 0.8 mL/min, and detection was carried out at a wavelength of 222 nm. The developed HPLC method showed an accuracy between 98% and 102%. The primary diffusion study of film‐forming spray was performed using the Franz vertical diffusion cell apparatus. It was observed that an average of 26.94% of drug releases at 24 h. This indicates the drug has a slower release rate and shows local pharmacological action. The Weibull dissolution model was more fitting with regression square 0.9953. Furthermore, the drug excipient compatibility study revealed no interactions as the only drug peak was found in the chromatographic method, indicating that the chosen excipients were appropriate for a stable formulation.

Development, validation and greenness assessment of environmentally friendly analytical methods for the quantification of lenalidomide in pharmaceutical formulations

AbstractLenalidomide is a drug that has immune-modulating, anti-angiogenic, and anti-inflammatory properties. In this study, we developed green HPLC and spectrophotometric methods to determine the concentration of lenalidomide in pure and pharmaceutical formulations. In the HPLC method, 10 mM potassium dihydrogen phosphate solution (pH: 2.0) and ethanol (50:50, V/V) were used as mobile phases, isocratic elution was applied at a flow rate of 1.0 mL min−1 and detection was made at 304 nm. In the spectrophotometric method, the spectral patterns of standard solutions in different solvents were comprehensively examined, the best spectra were obtained with ultrapure water, and a wavelength of 304 nm was selected for detection. Both methods have been validated according to ICH guidelines for various parameters. Correlation coefficients greater than 0.999 were determined for both methods in the concentration range of 5–30 μg mL−1. The developed methods were applied to commercial formulations, and comparisons of the results were made using the Student (t) test for means and the Fischer (F) test for standard deviations. No statistically significant difference was observed between the methods. The greenness evaluation of these methods was carried out using AGREE software. The developed methods are proposed as excellent environmental and operator-friendly alternatives for the quantification of Lenalidomide in pharmaceutical formulations.

Study of the Formation of Precursor Clusters in an Aqueous Solution of KH2PO4 by Small-Angle X-ray Scattering and Molecular Dynamics

The structure of an aqueous solution of potassium dihydrogen phosphate (KH2PO4, KDP) was studied by small-angle X-ray scattering (SAXS) and molecular dynamics (MD). According to SAXS data, the octameric species (KH2PO4)8 are formed in solution in addition to K+, (H2PO4)−, and KH2PO4, while the presence of other types of oligomers is not observed. When the temperature drops below the saturation temperature (~60 °C), the volume fraction of octamers increases sharply, reaching 50% at 4 °C. The results of MD calculations of the temporal stability relationships of dimers (KH2PO4)2, tetramers (KH2PO4)4, and octamers (KH2PO4)8 show that the dimers and tetramers disintegrate rapidly (50–100 ps), while the octamers remain stable. A comparative analysis of the bonds between the octamers and the KDP crystal lattice was carried out when the octamer was inserted during crystal growth in the directions [001] and [100]. The possible relationship of the obtained results with the changes in the anisotropy of growth rates (habitus) of KDP crystals at different degrees of supersaturation is discussed.

Development and validation of stability indicating UPLC methods for related substances and assay analyses of ricobendazole hydrochloride

Ricobendazole hydrochloride is an active ingredient of a veterinary antiparasitic drug. The aim of this study was to investigate the degradation of ricobendazole hydrochloride under stress and stability testing conditions, for which we developed and validated the first stability indicating, specific, precise, accurate, and robust assay and related substances UPLC methods. The Acquity UPLC BEH C18 column was used for the related substances and assay analyses of ricobendazole hydrochloride, and the analyses were performed at 25 °C sample and 30 °C column temperatures with a 2 µL injection volume. In both methods, a mixture of water and methanol (60:40, v/v) was used as the diluent, mobile phase A was a phosphate buffer (50 mM potassium dihydrogen phosphate solution, pH 3.2 ± 0.05, adjusted with 10% o-phosphoric acid), and mobile phase B was a mixture of mobile phase A and acetonitrile (50:50, v/v). For the analysis of related substances, a gradient elution system was used at a flow rate of 0.4 mL/min for 35 min with a detection wavelength of 220 nm, while for the assay analysis; a gradient elution system was used at a flow rate of 0.3 mL/min for 15 min with a detection wavelength of 290 nm. The calibration curves showed excellent linearity with high R-squared (R2) values for each compound, ricobendazole (0.9998, 0.249 – 3.740 µg/mL), ricobendazole amine (0.9998, 0.255 – 3.819 µg/mL), albendazole (0.9998, 0.255 – 7.646 µg/mL), and albendazole sulfone (1.0000, 0.251 – 15.090 µg/mL) indicating a strong correlation between the concentrations of the compounds and their respective peak areas in the UPLC analysis. The method showed excellent accuracy with relative standard deviation values of less than 2.5%. The stress and photostability studies showed that ricobendazole hydrochloride was insensitive to daylight and UV radiation and showed significant degradation at elevated temperature (85 °C, 9 days) and under all hydrolysis and oxidation conditions. The major impurity was ricobendazole amine under thermal and hydrolysis conditions, while albendazole sulfone was the major oxidative impurity.

Quality by design paradigm for optimization of green stability indicating HPLC method for concomitant determination of fluorescein and benoxinate

A green, robust and fast stability indicating chromatographic method has been developed for concomitant analysis of fluorescein sodium and benoxinate hydrochloride in the presence of their degradation products within four minutes. Two different designs including fractional factorial and Box–Behnken designs were implemented for screening and optimization steps, respectively. The optimum chromatographic analysis was achieved using a mixture of isopropanol and 20 mM potassium dihydrogen phosphate solution (pH 3.0) in the ratio 27:73 as mobile phase. The flow rate was 1.5 mL/min and column oven temperature was 40 °C. Chromatographic analysis was performed on Eclipse plus C18 (100 mm × 4.6 mm × 3.5 μm) column with DAD detector set at 220 nm. A linear response was acquired over the range of 2.5–60 μg/mL and 1–50 μg/mL for benoxinate and fluorescein respectively. Stress degradation studies were executed under acidic, basic, and oxidative stress conditions. The method was implemented for quantitation of cited drugs in ophthalmic solution with mean percent recovery ± SD of 99.21 ± 0.74 and 99.88 ± 0.58 for benoxinate and fluorescein respectively. The proposed method is more rapid and eco-friendly compared to the reported chromatographic methods for determination of cited drugs.

Effect of Superhydrophobic Surface on Corrosion Resistance of Magnesium-Neodymium Alloy in Artificial Hand Sweat

A superhydrophobic surface can endow metals with some intriguing characteristics such as self-cleaning behavior. In this study, a simple solution-immersion method based on the concept of predesigned corrosion is developed to enhance the corrosion resistance of a magnesium-neodymium alloy. The Mg alloy is directly soaked in potassium dihydrogen phosphate solution with the addition of ultrasound, and a layer of rough but dense coating is uniformly formed on the Mg-Nd alloy after the immersion process, which is mainly composed of MgHPO4∙3H2O. A superhydrophobic surface with an average wetting angle of 150.5° and a sliding angle of about 4.5° can be obtained on the Mg alloy by further chemical surface modification with perfluorodecyltriethoxysilane. This superhydrophobic surface has an interesting self-cleaning effect as well as good corrosion resistance in artificial hand sweat. In brief, this study provides a feasible way to prepare a superhydrophobic surface on the Mg-Nd alloy and reveals the effect of a superhydrophobic surface on the corrosion behavior of the Mg-Nd alloy, offering new technical insights into the corrosion protection of magnesium alloys.

Simultaneous Determination of nicotinamide, kojic acid, Tranexamic acid, raspberry glycoside, azelaic acid, magnesium ascorbate phosphate and β-Arbutin in whitening cosmetics by UPLC-MS/MS

A UPLC-MS/MS method was developed for simultaneous determination of 7 whitening ingredients: nicotinamide, kojic acid, Tranexamic acid, raspberry glycoside, azelaic acid, magnesium ascorbate phosphate and β-Arbutin in cosmetics. The whitening active components were extracted from cosmetics by supersonic extraction with sodium chloride and dichloromethane to disperse the sample, and supersonic extraction with 0.015 mol/L potassium dihydrogen phosphate solution purified by HLB solid phase extraction column, scanned and detected by electrospray ionization source with positive and negative ion alternate scanning mode and multiple reaction monitoring mode. The results showed that the whitening active ingredients were separated within 3 minutes, with a good linear relationship (R>0.999), and the detection limit was 0.10mg/kg~0.75mg/kg. The recoveries (n=6) were 78.84%-104.85%, and the RSDs were 0.24%-11.35%. This method is suitable for the rapid determination of whitening active ingredients in cosmetics.

Temperature Behavior of Precursor Clusters at the Pre-Crystallization Phase of K(H2PO4) Studied by SAXS

Elementary building blocks for the growth of KDP crystals were established. The solution of potassium dihydrogen phosphate (KH2PO4–KDP) has been experimentally studied by the small-angle X-ray scattering (SAXS) method. The analysis of SAXS data in the temperature range of 2.5–90 °C using a set of models of 3D fragments of the crystal structure showed that the saturated solution contains above K+, H2PO4− and KH2PO4 monomers, as well as mainly octamers. The 3D model of the octamer isolated from the crystal structure has dimensions of 17.443 Å along the [001] axis and 5.963 Å along the [100] and [010] axes. As the temperature is decreased, starting from the saturation temperature of the solution, the volume fraction of octamers sharply increases while the volume fraction of monomers decreases. The results indicate that the monomers and octamers represent major components in the solution with the presence of minor populations of other oligomers. The significant dominance of octamers in the supersaturated solution indicates that they are elementary building blocks for the growth of KDP crystals of tetragonal modification.

Дослідження профілів розчинення таблеток Амлодипіну з еналаприлом

забезпечення якості при виробництві лікарських препаратів є всеохоплюючою концепцією. Якість лікарських засобів має бути гарантована на всіх стадіях виготовлення – від розроблення, дослідження й виробництва до впровадження та оптимального застосування. Все це закладено у вимоги низки належних практик: GMP, GLP, GCP, GDP, GPP, GSP. Велике значення при розробці твердих лікарських форм надається вивченню швидкості вивільнення діючих речовин та в середовищах з різним показником кислотності. Для оцінки якості розроблених комбінованих таблеток Амлодипіну з еналаприлом, прогнозування швидкості вивільнення діючих речовин з них, а відповідно прояву терапевтичної дії на організм. Метою роботи було вивчити профілі розчинення таблеток Амлодипіну з еналаприлом у порівнянні з оригінальними монопрепаратами. Обʼєктами дослідження були розроблений засіб Амлодипіну з еналаприлом, таблетки 5 мг/5 мг та відповідні оригінальні монопрепарати: Норваск (Pfizer Manufacturing Deutschland GmbH), таблетки 5 мг (амлодипін) та Берліприл (BERLIN-CHEMIE), таблетки 5 мг (еналаприл). Дослідження проводилися згідно Фармакопейних вимог з використанням приладу для розчинення USP I (лопаті). Середовища розчинення – 900 мл буферних розчинів рН 1,2, рН 4,5 і рН 6,8. Аналіз здійснювали методом високоефективної рідинної хроматографії. В якості рухомої фази застосовували розчин калію дигідрофосфату у воді (рН 4,0). Детектування проводили за довжини хвилі 215 нм. Було здійснено порівняльні дослідження кінетики розчинення засобу Амлодипін з еналаприлом, таблетки 5 мг/5 мг з кінетикою розчинення оригінальних монопрепаратів Норваск (Pfizer Manufacturing Deutschland GmbH), таблетки 5 мг та Берліприл (BERLIN-CHEMIE), таблетки 5 мг. Встановлено, що через 15 хв. в середовищі рН 6,8 еналаприлу малеат вивільняється з розроблених комбінованих таблеток лише на 83,6 %, а впродовж 30 хв. спостерігалося повне вивільнення обох активних фармацевтичних інгредієнтів у всіх досліджуваних середовищах. Виявлено високе значення фактора подібності профілю розчинення розроблюваного препарату Амлодіпин з еналаприлом, таблетки 5 мг/5 мг до оригінальних монопрепаратів: рН 1,2: амлодипін – 92,3, еналаприл – 86,5; рН 4,5: амлодипін – 94,8, еналаприл – 86,3; рН 6,8: амлодипін – 96,2, еналаприл – 80,2. Було визначено, що біофармацевтичні фактори, до яких належать фізико-хімічні властивості амлодипіну та еналаприлу, склад допоміжних речовин, особливості технологічного процесу, мають вплив на кінетику розчинення досліджуваного препарату на основі амлодипіну та еналаприлу. Отже, запропоновані комбіновані таблетки Амлодипіну з еналаприлом аналогічні відповідним референтним монопрепаратам і можуть бути використані в експериментальній і практичній медицині.

Development and validation of a reversed-phase high-performance liquid chromatography-ultraviolet method for abemaciclib-related substance detection in bulk drugs.

Abemaciclib is an effective selective cyclin-dependent kinases 4 and 6 inhibitors for cancer therapy. The abemaciclib-related substances influence its efficacy and safety, and are important in process preparation studies and quality control. Thus, a reversed-phase high-performance liquid chromatography method was developed and validated for the detection of related substances in its bulk drug. The separation of abemaciclib and related substances was performed on a Phenomenon Gemini C18 column (4.6 × 250 mm, 5 μm) with a flow rate of 1.0ml/min. The ultraviolet detection wavelength was 280 nm. Mobile phase A was composed of a mixed solution of aqueous solution and acetonitrile (9:1, v/v). The aqueous solution (pH 2.5) contained 0.025-mM potassium dihydrogen phosphate solution and 0.4% triethylamine. Mobile phase B was composed of acetonitrile. This novel method exhibits good system suitability, specificity, precision, stability, linearity (0.1-20 μg/ml), repeatability, and durability. Among abemaciclib and related substances, the lowest limit of detection and quantitation were 0.02 and 0.06 μg/ml, respectively, for abemaciclib. The recovery rates for related substances were above 95%. In addition, a novel degradation product was found during the process. In summary, a reliable reversed-phase high-performance liquid chromatography method was developed for abemaciclib-related substance detection in bulk drugs.

Phytoremediation of arsenic contaminated soil based on drip irrigation and intercropping

A directional leaching in drip irrigation along with intercropping was developed for enhanced phytoremediation of soils contaminated with arsenic (As). Spatiotemporal variations of As levels in soil and effects of irrigation eluents on As migration were analyzed in drip irrigation. Moreover, accumulated levels of As in Zea mays L. and Brassica rapa L. ssp. chinensis (the intercropping species) under drip irrigation and flood irrigation were compared to evaluate the enhancement on phytoremediation by drip irrigation. Results showed that As exhibited a directional migration in soil under drip irrigation, in which the solution of potassium dihydrogen phosphate (PDP) as the eluent significantly promoted As directional migration in soil. Compared to the flood-irrigated intercropping treatments, the As levels in crops (Brassica rapa L. ssp. chinensis) decreased significantly and that of remediating plants (Zea mays L. seedlings) increased significantly under the drip-irrigated intercropping condition. Drip irrigation coupled with intercropping dramatically reduced the risk of As contamination in crops and improved the phytoremediation of As-contaminated soil. PDP further enhanced the disparate effect of drip irrigation on As accumulation by crops and remediation plants.

Enhanced corrosion resistance of magnesium-neodymium alloy in simulated concrete pore solution by predesigned corrosion product

The natural surface films on Mg alloys can’t provide enough corrosion protection in aqueous solutions compared to those on Al alloys and Ti alloys. In this study, a strategy is proposed for corrosion protection of Mg alloys by transforming corrosion products into protective coatings. Here, a magnesium-neodymium alloy is immersed in potassium dihydrogen phosphate solution at 50 °C for 4 h. Following this simple corrosion process, a layer of uniform MgHPO4.3 H2O coating with a thickness of about 20 µm is formed on the Mg alloy. Electrochemical test and long-term immersion test reveal that this coating significantly improves the corrosion resistance of the Mg-Nd alloy in Cl--containing simulated concrete pore solution. In summary, it indicates that some corrosion products can be designed to be transformed into protective coatings, providing new technical insights pertaining to the corrosion protection of magnesium alloys.

A comparative study of HPLC and UV spectrophotometric methods for oseltamivir quantification in pharmaceutical formulations

Abstract Oseltamivir is an antiviral drug and is used in the treatment of all influenza viruses. It is the most effective antiviral option against all influenza viruses that can infect humans. UV and LC methods have been developed and validated according to ICH guidelines for various parameters like selectivity, linearity, accuracy, precision, LOD and LOQ, robustness for the quantitative determination of oseltamivir in pharmaceutical formulations. LC method has been performed using reverse phase technique on a C-18 column with a mobile phase consisting of 20 mM potassium dihydrogen phosphate solution and acetonitrile (60:40, v/v) at 25 °C. The mobile phase flow rate was 1.2 mL min−1. For the determination of oseltamivir, UV spectrum has been recorded between 200 and 800 nm using methanol as solvent and the wavelength of 215 nm has been selected. Both methods have demonstrated good linearity, precision and recovery. No spectral and chromatographic interferences from the capsule excipients were found in UV and LC methods. In both methods, correlation coefficients were greater than 0.999 within a concentration range of 10–60 mg mL−1 using UV and LC. Intra-day and inter-day precision with low relative standard deviation values were observed. The accuracy of these methods was within the range 99.85–100.17% for LC and from 99.26 to 100.70% for UV. Therefore UV and LC methods gave the most reliable outcomes for the determination of oseltamivir in pharmaceutical formulation.

Separation and determination of D-malic acid enantiomer by reversed-phase liquid chromatography after derivatization with (R)-1-(1-naphthyl) ethylamine

L-Malic acid is the Active Pharmaceutical Ingredient of the latest generation of compound electrolyte injection (STEROFUNDIN ISO, Germany) and plays a very important role in the rescue of critically ill patients. The optical purity of L-malic acid is a Critical Quality Attributes. A new reversed-phase high performance liquid chromatography (RP-HPLC) method for pre-column derivatization of D-malic acid enantiomer impurity in L-malic acid bulk drug was established. The derivatization reaction was carried out using (R)-1-(1-naphthyl)ethylamine ((R)-NEA) as a chiral derivatization reagent. The Kromasil C18 column was used with a detection wavelength of 225 nm, a flow rate of 1.0 mL·min-1, and a column temperature of 30 °C. The mobile phase was acetonitrile-0.01 mol·L-1 potassium dihydrogen phosphate solution (containing 20 mmol·L-1 sodium heptanesulfonate, adjusted to pH 2.80 with phosphoric acid) (at a ratio of 45:55) and the resolution of D-malic acid and L-malic acid derivatization products reached 1.7. The proposed method possesses the advantages of simple operation, mild conditions, stable derivatization products and low cost. Also it gave better separation and was more accurate than previous methods.

The Determination of Metronidazole and Chlorhexidine Gluconate in Metronidazole and Chlorhexidine Lotion by HPLC

Objective “To establish an HPLC method for the determination of metronidazole and chlorhexidine gluconate in metronidazole and chlorhexidine lotion. Method Using Agilent Eclipse-XDB-C18 chromatographic column, with 0.05 mol·L-1 potassium dihydrogen phosphate solution 1000 ml plus 13.2 ml 10% tetrabutylammonium hydroxide aqueous solution (pH adjusted to 3.5 by phosphoric acid)-acetonitrile (77:23) as Mobile phase, detection wavelength 230 nm. Results The two components could be separated well. The linear ranges of metronidazole and chlorhexidine acetate were 36.33~59.04 μg·ml-1 (r = 0.9994) and 35.45~220.11 μg·ml-1 (r = 1).); The average recoveries were 100.6% and 100.5 %, and the RSD were 0.42% and 0.58%. Conclusion: The method is simple and specific, and the result is more accurate and reliable. Which is suitable for simultaneous determination of two components in compound preparations.

Development of a Liquid Chromatographic Method for Apomorphine Hydrochloride Quantitation in the Active Pharmaceutical Ingredients and in the Dosage Forms

Apomorphine is currently used as a dopamine agonist to treat advanced Parkinson Disease. In the present study, we developed a sensitive, simple, reliable, and robust HPLC method for quality control of apomorphine hydrochloride in bulk drug and pharmaceutical formulations. C18 column was used for separation. Isocratic elution was performed using mobile phase A: 50 mM potassium dihydrogen phosphate solution (pH:3 with ortho-phosphoric acid), B: acetonitrile in the ratio of 85:15 (A: B), and the mobile-phase flow rate was kept at 1 mL min-1. Analyses were carried out at 272 nm using a UV detector. A perfect linear relationship between peak-area versus drug concentration in the range of 10‑100 μg mL-1 was observed (r2, 0.9999). It has been found that the developed method is sensitive (Detection and quantification limits were determined as 1.3 μg mL-1 and 3.8 μg mL-1, respectively), precise (RSD

DEVELOPMENT AND VALIDATION OF METHODS FOR QUANTITATIVE DETERMINATION OF ACTIVE PHARMACEUTICAL SUBSTANCES IN NASAL SPRAY

Intranasal administration of H1-histamine receptor blockers may be a promising approach to the treatment of allergic rhinitis. Earlier, an original composition of a nasal spray containing fexofenadine hydrochloride and ammonium glycyrrhizinate and demonstrating a high level of therapeutic efficacy, was developed.The aim of the study was to develop and validate a method of the quantitative determination of active pharmaceutical ingredients fexofenadine hydrochloride and ammonium glycyrrhizinate in a spray for intranasal administration.Materials and methods. During the development and validation of the method of the fexofenadine hydrochloride and ammonium glycyrrhizinate quantitative determination in a nasal spray, the method of high performance liquid chromatography was used: a Dionex Ultimate 3000 UV chromatograph with a Luna C18 column (2) containing octadecylsilicagel with a 5 μm grain size as a sorbent. The analysis and validation procedures were performed in accordance with the requirements of the State Pharmacopoeia of the Russian Federation, the XIVth edition.Results. The study showed that for the simultaneous quantitative determination of fexofenadine hydrochloride and ammonium glycyrrhizinate, the optimal elution regime is a gradient mode with a mobile phase containing 50 mmol/L potassium dihydrogen phosphate solution with methanol (45:55), which ensured the separation of the components in the 20 minutes interval. The validation procedures showed that the developed methodology correspond to all the criteria of validity in terms of the following indicators: correctness, precision, specificity and linearity in the analytical area.Conclusion. The obtained results indicate the possibility of using the method of high-performance liquid chromatography in a gradient elution mode with a mobile phase of the composition of a 50 mmol/L solution of potassium dihydrogen phosphate with methanol (45:55) for the simultaneous quantitative determination of active pharmaceutical ingredients – fexofenadine hydrochloride and ammonium glycyrrhizinate as parts of a promising nasal spray for the allergic rhinitis treatment.

Determination of Impurities in Perampanel Bulk Drugs by High- Performance Liquid Chromatography and Gas Chromatography

Background: High-performance liquid chromatography (HPLC) method has been used to detect related impurities of perampanel. However, the detection of impurities is incomplete, and the limits of quantification and detection are high. A sensitive, reliable method is in badly to be developed and applied for impurity detection of perampanel bulk drug. Objective: Methodologies utilising HPLC and gas chromatography (GC) were established and validated for quantitative determination of perampanel and its related impurities (a total of 10 impurities including 2 genotoxic impurities). Methods: The separation was achieved on a Dikma Diamonsil C18 column (250 mm × 4.6 mm, 5 μm) with the mobile phase of 0.01 mol/L potassium dihydrogen phosphate solution (A) and acetonitrile (B) in gradient elution mode. The compound 2-bromopropane was determined on an Agilent DB-624 column (0.32 mm × 30 m, 1.8 μm) by electron capture detector (μ-ECD) with split injection ratio of 1:5 and proper gradient temperature program. Result: Both HPLC and GC methods were established and validated to be sensitive, accurate and robust according to the International Council for Harmonization (ICH) guidelines. The methods developed were linear in the selected concentration range (R2≥0.9944). The average recovery of all impurities was between 92.6% and 103.3%. The possible production mechanism of impurities during the synthesis and degradation processes of perampanel bulk drug was also discussed. Five impurities were analyzed by liquid chromatography–mass spectrometry (LC-MS). Moreover, two of them were simultaneously characterized by LC-MS, IR and NMR. Conclusion: The HPLC and GC methods were developed and optimized, which could be applied for quantitative detection of the impurities, and further stability study of perampanel.

Synthesis of pure potassium pentaborate (KB5) from potassium dihydrogen phosphate (KH2PO4) and colemanite

In this study, after specifying theoretical reaction conditions required for the chemical reaction, potassium pentaborate (KB5) was synthesized from the potassium dihydrogen phosphate ( $${\text{KH}}_{2} {\text{PO}}_{4}$$ ) solution and raw colemanite ( $${\text{Ca}}_{2} {\text{B}}_{6} {\text{O}}_{{11}} \cdot 5{\text{H}}_{2} {\text{O}}$$ ) ore. The slow evaporation solution method was used at 25 °C. The effect of time (6–18 h) on crystallization was studied. Synthesized minerals were characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), RAMAN spectroscopy, and scanning electron microscopy (SEM). The results according to XRD, FT-IR, RAMAN, and SEM analyses proved that the synthesized product was potassium pentaborate ( $${\text{KB}}_{5} {\text{O}}_{8} \cdot 4{\text{H}}_{2} {\text{O}}$$ ) mineral with ICSD: 96-026-1927 pdf code. As a result, the cost was reduced by using raw boron ore, colemanite, and KB5 was obtained in a shorter time and at a lower temperature.