Dissolution Samples Research Articles

Investigational Study of Mesalamine Dissolution Discrepancy: Utilization of Hyphenated Ultrahigh Performance Liquid Chromatography‐Charged Aerosol Detection‐High‐Resolution Mass Spectrometry

ABSTRACTPentasa (mesalamine/MSLM) is a widely prescribed delayed‐release capsule formulation for the treatment of inflammatory bowel disease. During dissolution study of Pentasa through ultraviolet (UV) spectroscopy, an unusual end‐release of about 110% has been observed. Initial liquid chromatography‐UV (LC‐UV) analyses of these dissolution samples confirmed three prominent peaks other than MSLM with a significant area percentage. Further systematic investigation was carried out by incubating active pharmaceutical ingredient in dissolution media for a longer duration and at elevated temperature followed by analysis through an inverse gradient LC‐charged aerosol detector (CAD). LC–high‐resolution mass spectrometry (HRMS) and online hydrogen‐deuterium exchange (HDX) mass spectrometry were also employed to identify and characterize these artifact products. The area % of prominent artifacts in LC‐UV was found to be way significant when compared to the area % obtained through inverse LC‐CAD, as CAD quantifies the peaks independent of the UV wavelength of absorbance. Inverse LC‐CAD was suitable to determine the relative response factor, whereas LC‐HRMS/MS and online HDX‐MS supported the characterization of these artifacts. These artifacts were found to be trimers, tetramers of MSLM formed due to polymerization, imparting additional pi‐bonds resulting in high UV absorptivity. These techniques when used in combinations serve complimentary to each other during such investigations.

Formulation and evaluation of physical, chemical and sensory properties of instant functional beverage powder containing Pathum Thani fragrance rice, soy protein and milk powder

The purpose of this study was to determine the influence of proportion and ratio of the following main ingredients comprising Pathum Thani fragrance rice powder, soy protein and milk powder on physicochemical properties and sensory characteristics of instant functional beverage powder. The experimental procedures consisted of prerequisite processing steps of cooking, drying, crushing and mixing all ingredients. The design was used to produce a total of ten samples of powdered beverage products. Whereas, dry samples and complete dissolution samples were analyzed for their physicochemical properties and sensory characteristics. Results indicated that the prepared beverage powder with various ratios of ingredient combinations delivered significant impact on their physical chemical and sensory characteristics. Principal component analysis (PCA) was implemented to group the attributes into three key dimensions that explained 76.51% of the total variance. Furthermore, Partial least squares regression (PLSR) was employed as a multivariate statistical tool to accurately determine carbohydrate, fiber, L* (dissolve), a* (dissolve) and b* (dissolve) as key drivers of liking. Having the highest consumer satisfaction levels and highest average liking scores of all sensory characteristics, the optimum formulation for instant functional beverage powder was formula 10 containing 23.34% of Pathum Thani fragrance rice powder, 13.33% of soy protein and 13.33% of milk powder, 20% of sugar, 10% of cocoa powder, 10% of malt powder, 5% of non-dairy cream powder and 5% inulin powder. More importantly, these research findings may influence decisions at many levels in increasing consumer acceptance of the product, manufacturing healthier products for people, and adding value to products of agriculture.

In vitro dissolution equivalence of Jordanian sildenafil generics via validated, stability-indicating HPLC method.

This study was conducted to compare dissolution profiles of four Jordanian registered sildenafil (SDF) products to the originator. Dissolution samples were analyzed utilizing a validated and stability-indicating HPLC method in human plasma. Validation was performed forspecificity, linearity, limit of detection, lower limit of quantification, precision, trueness and stability. SDF was extracted from plasma samples using liquid-liquid extraction. The analysis wasperformed utilizing isocratic elution on C18 column with 1.0ml/min flow rate. The regression value was ∼0.999 over 3days with drug recovery between86.6 to 89.8%with 10ng/ml lower limit of quantitation. This method displayed a good selectivity of SDF with improved stability under various conditions. The method was used for SDF quantification in dissolution medium. Similarity factors for local products varied according to the used mediums, but all SDF local products passed the dissolution in vitro test since all of them showed a released of >85% after 60min at the dissolution mediums.

Profiling of 3-Formyl rifamycin (3-FR) from sintered fixed dose combinations (SDCs) of rifampicin and isoniazid by using RP-HPLC, LC-ESI-QTOF and UPLC/MS/MS

The rapid and severe decomposition of rifampicin in the presence of isoniazid (INH) in a gastric acidic pH environment is a well-reported phenomenon. It is important to note that the significant decomposition problem of RIF has an impact on its bioavailability, which becomes a major issue in fixed dose combinations (FDCs). In this degradation process, RIF will undergo acid hydrolysis and form 3-FR, an acid degradation product of RIF. Further, it will react with INH and form an insoluble iso-nicotinoyl hydrazone (HYD). The formed HYD is probably not stable in the acidic condition, so it will further convert into INH and 3-FR. Consequently, the generation of 3-FR in the acidic stomach environment can be a critical factor contributing to a substantial decline in RIF bioavailability and warrants careful consideration. Hence, it is imperative to explore the presence of 3-FR not only in in vitro dissolution samples but also in in vivo plasma samples. Therefore, the current study focused on the chemical analysis of 3-FR using additively manufactured sintered drug combinations (SDCs) to evaluate its formation, release and qualitative absorption in both in vitro and in vivo settings. High-performance liquid chromatography (HPLC) and liquid chromatography-electrospray ionization quadrupole time-of-flight high-resolution mass spectrometry (LC-ESI-QTOF-MS/MS) were employed for analytical investigations. The developed LC/MS-MS method was employed to investigate the presence of 3-FR in the rabbit's plasma following a single oral administration of SDCs. The study revealed the significant presence of 3-FR in both the in vitro and in vivo plasma samples obtained from the SDCs of RIF and INH. This finding indicates the potential of altering the strategy through additive manufacturing of pH-dependent SDCs to address the critical issue of RIF.

Characterization and stability analysis of metformin HCl microcapsules formulated by complex coacervation technique

Objective: Metformin hydrochloride possesses a shorter sort of biological half-life of 1.5–1.6 h with having the absolute type of bioavailability that ranges between 50-60%, the moment it is administered orally. Reduced GIT disturbances and low bioavailability can be optimized by developing microencapsulation of metformin that could prove beneficial. Method: Paraffin oil had been used in obtaining specific types of primary emulsions, whereas the material that was used in the coating of microencapsulation had been identified as sodium alginate. In the process of complex coacervation, a substance known as Tween 20 was used as a surfactant in enhancing the stability of W/O/W double emulsion. Five different formulations with different concentrations of sodium alginate were tested. Result: Metformin's microencapsulation inside certain types of optimized atmosphere tends to ensure the specific size of 1 am of microcapsules in a combined form, and encapsulation efficiency reaches up to 84%. FTIR measurements have been used to determine the interaction between drug and polymer. The qualitative analysis result from FTIR ensures that the quality and effectiveness of the drug have been preserved. A calibration curve was used to estimate drug conc. from dissolution samples and kinetic analysis demonstrated anomalous release pattern. The test for drug content yielded ˃95% of concentration. Conclusion: Results extracted tend to tell us that specific complex coacervation that is using sodium alginate in wall material was a viable method that is used in the microencapsulation process of metformin hydrochloride.

Characterization and stability analysis of metformin HCl microcapsules formulated by complex coacervation technique

Objective: Metformin hydrochloride possesses a shorter sort of biological half-life of 1.5–1.6 h with having the absolute type of bioavailability that ranges between 50-60%, the moment it is administered orally. Reduced GIT disturbances and low bioavailability can be optimized by developing microencapsulation of metformin that could prove beneficial. Method: Paraffin oil had been used in obtaining specific types of primary emulsions, whereas the material that was used in the coating of microencapsulation had been identified as sodium alginate. In the process of complex coacervation, a substance known as Tween 20 was used as a surfactant in enhancing the stability of W/O/W double emulsion. Five different formulations with different concentrations of sodium alginate were tested. Result: Metformin's microencapsulation inside certain types of optimized atmosphere tends to ensure the specific size of 1 μm of microcapsules in a combined form, and encapsulation efficiency reaches up to 84%. FTIR measurements have been used to determine the interaction between drug and polymer. The qualitative analysis result from FTIR ensures that the quality and effectiveness of the drug have been preserved. A calibration curve was used to estimate drug conc. from dissolution samples and kinetic analysis demonstrated anomalous release pattern. The test for drug content yielded ˃95% of concentration. Conclusion: Results extracted tend to tell us that specific complex coacervation that is using sodium alginate in wall material was a viable method that is used in the microencapsulation process of metformin hydrochloride.

A lyophilized surfactant-based rutin formulation with improved physical characteristics and dissolution for oral delivery

Rutin (RUT) is a phytochemical flavonoid with numerous therapeutic potentials including antihypertension, cardioprotective, neuroprotective, and anti-cancer activities. Its clinical use is inhibited due to its poor aqueous solubility and permeability over oral administration. The present study aimed to overcome these problems through micellization and entrapment of RUT in solid dispersion (SD) using Poloxamer (POL) 407 and 188 as surfactant-based matrices. The RUT/SD formulations were prepared in serial drug loading concentrations in weight percentage to the total solid. The physical properties of the formed RUT/SD solids were characterized by several methods including polarizing microscopy, differential thermal analysis (DTA), X-ray diffractometry (XRD), scanning electron microscopy (SEM) and dissolution study. The dissolution test was performed using a paddle dissolution apparatus and samples were analyzed using UV spectrophotometry. Polarized microscope confirmed that the optical behaviors of the RUT/SD implied a formation of miscible RUT with POL matrices. The morphology of RUT/SDs varied from porous matrices with craters to smoother surfaces as a function of RUT concentrations. XRD and DTA data exhibited that RUT existed as partially amorphous. These data indicated that the higher concentration of RUT in the RUT/SD formulations, the higher amorphous proportion of the RUT in the solid state. Henceforth, this led to an increase in the percentage of dissolved RUT from the developed RUT/SD formulations at 94 to 100% compared to pure RUT at only < 35% within an hour. The present study disclosed the successful improvements in the physical characteristics of the RUT/SD formulations and their potencies for the future development for oral formulation.

Dissolution Assay of Bupropion/Naltrexone Hydrochloride Salts of Bilayer Composition Tablets Following the Development and Validation of a Novel HPLC Method

Compounded medicinal products containing bupropion hydrochloride (BUP·HCl) and naltrexone hydrochloride (NTX·HCl) are available as adjunct therapy for the management of weight in obese/overweight adults. The present work describes the development and validation of a novel RP-HPLC method for a simultaneous quantitation during the dissolution of both drugs from compounded bilayer composition tablets. The method involves a Nucleosil 100-3 C-18 column (4.6 × 150 mm) and a mobile phase of a 70%/30% v/v ACN/KH2PO4·H2O aqueous solution of a 5 mM concentration. The flow rate was set at 1.35 mL/min and the detection was conducted using UV spectrophotometry (λmax 214 nm). The method was validated according to the ICH guidelines and fulfilled the specifications for the specificity, linearity, accuracy, precision and stability for both the sample and standard solutions. Furthermore, the robustness of the method was evaluated by applying a fractional factorial experimental design and by utilizing both graphical and statistical approaches to identify the HPLC factors that should be strictly controlled during the analysis. The method proved to be suitable for the analysis of the dissolution samples and, consequently, the release of BUP·HCl and NTX·HCl from the formulations.

Development and validation of UV spectroscopic method for estimation of sacubitril and valsartan combination (LCZ696) in bulk and pharmaceutical tablet dosage forms

Sacubitril and valsartan combination is a member of a new class of agents called angiotensin receptor-neprilysin inhibitors (ARNI’s) which combine neprilysin inhibitor and angiotensin receptor blocker (ARB). It is currently indicated for treating patients with heart failure with reduced ejection fraction (HFrEF) in place of an angiotensin-converting enzyme (ACE) inhibitor or ARB alone. The aim of present investigation is to develop a simple UV spectrophotometric method for the determination of sacubitril and valsartan combination in its pure form and pharmaceutical tablet formulations in 0.1N HCl (pH 1.2) and pH 6.8 phosphate buffer, and further to validate the developed method. The combination in bulk was estimated at λmax of 253 nm in 0.1N HCl and pH 6.8 phosphate buffer. The observed λmax was close to the calculated λmax predicted using Woodward Fieser rules. The method was validated using analytical parameters like linearity, precision, and accuracy as per guidelines laid down by International Conference on Harmonization (ICH). Beer’s law was obeyed in the concentration range of 1–20 μg/mL in both media with correlation coefficient value of 0.999. The accuracy was found between 99-101% in both media. The method showed good reproducibility with % RSD values less than 2. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.5353 μg/mL, 1.6222 μg/mL in 0.1N HCl and 0.395 μg/mL, 1.198 μg/mL in pH 6.8 phosphate buffer respectively indicating its sensitivity. Molar absorptivity of the drug was found to be 3.84x104, 3.68x104 L mole-1 cm-1 and Sandell’s sensitivity values were found to be 0.0249 and 0.025 μg cm-1/0.001 absorbance unit in 0.1 N HCl and pH 6.8 phosphate buffer respectively. The assay values of the drugs in pharmaceutical dosage forms were also found close to the labelled claim. The results demonstrated that the procedure is accurate, precise, and reproducible besides being simple, economical, and less time consuming and hence, suitably applied for routine analysis of sacubitril and valsartan combination in bulk, marketed tablet dosage forms and in vitro dissolution samples.

Simultaneous Evaluation of Dissolution and Absorption Study of Compound Danshen Tablets and Capsules Based on Cellular Electrical Sensing Model.

This study explores the dissolution mechanism and absorption process of compound Danshen tablets (CDTs) and compound Danshen capsules (CDCs) in vitro. Taking the cell index as the evaluation index of dissolution and absorption of multi-component solid preparations of CDTs and CDCs, it breaks through the idea of traditional research. We used real-time cell-based assay (RTCA) to provide a new idea and method for the consistency evaluation of traditional Chinese medicine (TCM) compound preparations. The drug dissolution and absorption simulation system (DDASS) was established to obtain the dissolution and absorption samples of compound Danshen solid preparations at different time points. The cell index (CI) of the sample to H9C2 cells was detected by RTCA technology, and the dissolution and absorption percentage were calculated based on this index to obtain the dissolution and absorption kinetics model. Meanwhile, one batch of tablets and one batch of capsules (batch numbers ZKC1816 and 202101001) were selected to conduct the overall animal pharmacodynamic experiment to verify the feasibility of drug effect evaluation with cell index as an indicator. The best fitting model of dissolution curves of each batch of CDTs and CDCs is the Weibull model. There was a good correlation (r > 0.86) between the dissolution-absorption-pharmacodynamic curve. Based on RTCA technology, we have established the comprehensive evaluation method for cell biology of compound Danshen solid preparations in line with the overall concept of TCM and a synchronous evaluation system of dissolution and absorption in vitro of new TCM compound solid preparations.

Standardized Analytical Procedure for Routine Testing of Amlodipine Besilate and Enalapril Maleate Simultaneously in In-vitro Samples

&gt;This study develops a standardized methodology for routine analysis of in-vitro samples of amlodipine besilate and enalapril maleate concurrently in immediate-release tablet dosage forms. UV-detection was performed at absorption maxima of 237.20 nm and 217.00 nm for amlodipine besilate and enalapril maleate, respectively; 6.8 pH phosphate buffer was used as dissolution media for 30 mintues, on USP II (Paddle) dissolution apparatus, at 50 RPM and 37.0 ± 0.5oC. The fallouts of the analysis were endorsed statistically. Results were satisfactory in the arrays of 1–19 μg mL-1 for amlodipine besilate and 1–9 μg mL-1 for enalapril maleate. The analysis results exhibited that the projected simultaneous method is modest, swift, precise, and accurate and used for the repetitive analysis of dissolution samples of amlodipine besilate and enalapril maleate in combined pharmaceutical dosage forms (tablets).

DEVELOPMENT AND VALIDATION OF DISSOLUTION METHOD FOR LINAGLIPTIN TABLETS

Objective: Linagliptin is used to treat type-2 diabetes. It is available singly as 5 mg tablet. Since there is no official dissolution method in Indian pharmacopeia, there is a need to develop a method for testing dissolution of linagliptin immediate release tablet. Methods: For establishing dissolution method, various media, volume of media, and speed of rotation were tried. Quantification of dissolution samples was carried out using HPTLC and UV method. TLC plate pre-coated with silica gel 60 F254 was used as stationary phase and mobile phase employed for the development of TLC plates was methanol: toluene in a ratio of 7:3 v/v. The mobile phase was allowed to travel a distance of 70 mm and saturation time set was 20 min. Detection wavelength set was 294 nm. Results: The most suitable condition for dissolution of linagliptin tablet was found to be dissolution apparatus type II (paddle) using 900 ml 0.1 N HCl as medium at speed of 75 rpm. The optimized chromatographic condition resulted in compact band at Rf value of 0.76±0.02. Conclusion: Both the chromatographic and spectroscopic methods which were used for quantification were found to be linear with r2 value of 0.9929 and 0.9918, respectively, accurate, precise, and robust.

Maraviroc Oral Disintegration Tablet: Analytical Design of Experiments (DoE) for Assessment and Comparison of In vitro Dissolution Profiles

Background: The bioavailability of a drug in a solid oral dose depends on its release from the drug product and its balance in dissolution. Compared with a reference drug, the newly developed formulation needs to establish bioequivalence by comparing the dissolution profile. Objective: To compare dissolution profiles of a newly developed maraviroc oral disintegration tablet and the reference Axentri® tablet. The current research was designed to establish and validate an integral analytical consistency by Quality by Design (QbD) approach to quantify maraviroc from dissolution samples using the RP-HPLC method. Methods: Maraviroc was formulated into an orally disintegrating tablet using a direct compression technique at different concentrations of sodium starch glycolate as super disintegrants and talc and magnesium stearate as glidants. The dissolution test in 0.1N HCl was performed according to standard procedures to predict bioequivalence. The results of dissolution tests were analyzed using the QbD Box Behnken Design multivariate RP-HPLC method. Results: The optimized formulation (F2) was selected as it showed 90% drug release in 5 min and a disintegration time of 22 sec with dissolution profiles to the marketed reference to meet the FDA requirements of f2 similarity factor statistics. The integrated analytical QbD method was statistically analyzed by ANOVA, counter-plot, and 3D response surface plots, which demonstrated that the model is statistically significant. The developed method was validated as per ICH guidelines Q2 (R1). Conclusion : In conclusion, maraviroc oral disintegrating tablets have been well prepared, and superior statement consistency is established by the implementation of the QbD analytical method for orally disintegrating tablet excellence and adoption.

A new reliable and rapid HPLC method for the simultaneous determination of amoxicillin and sulbactam pivoxil in pharmaceuticals. Application to both assay and dissolution samples

A new reliable and rapid HPLC method for the simultaneous determination of amoxicillin and sulbactam pivoxil in pharmaceuticals. Application to both assay and dissolution samples

Development, Validation, and Application of a High-Performance Liquid Chromatography Method for the Analysis of Dissolution Samples of Telmisartan and Rosuvastatin Calcium Double-Layer Formulation

Background: Telmisartan and rosuvastatin calcium fixed-dose combination double-layer tablet is used for hypertension and hyperlipidemia treatment. Owing to the critical problem in establishing the specificity, precision, and accuracy of the USP analysis method and simultaneous analysis method for both components, an analysis method that could be applied to researchers in the field is urgently needed. Objective: To develop and validate a reversed phase-high-performance liquid chromatography method for the quantitative analysis of dissolution samples of telmisartan and rosuvastatin calcium fixed-dose combination double-layer tablets, as a hypertension and hyperlipidemia treatment. Methods: The developed analysis method was validated according to USP Category I requirements. The validity of the quantitative assay of the dissolution test solution was determined based on the system suitability, specificity, linearity, accuracy, precision, and solution stability of the assay for the components. Results: The developed method was selective and precise. The retention times of telmisartan and rosuvastatin calcium was 8.1 min and 2.8 min, respectively, and system suitability was 0.217 and 0.17, respectively. Both components showed linearity at 10–120% concentration. The accuracy and precision were also within acceptable limits. The drugs in the dissolution samples were stable for a long time, no interaction occurred between the excipients and active pharmaceutical ingredients, and no interference was observed in the analysis. Conclusion: The quantitative analysis of the double-layered formulation of telmisartan and rosuvastatin calcium was accurate, selective, and precise. Therefore, this method can be recommended for use in the industrial quality control of telmisartan and rosuvastatin calcium formulations.

RP-HPLC METHOD FOR ESTIMATION OF LORNOXICAM IN TABLETS AND IN DISSOLUTION SAMPLES USING MASS SPECTROMETRIC COMPATIBLE BUFFERS

A selective and sensitive reverse phase High Performance Liquid Chromatographic method has been developed and validated for the estimation of lornoxicam in bulk, pharmaceutical dosage forms and in dissolution samples. The analysis was performed isocratically on an Inertsil column (250* 4.6 mm, 5 µm) using a mass spectrometric compatible mobile phase of 10 mM ammonium acetate: acetonitrile (50:50 V/V) at a flow rate of 1 mL/min.The detection wavelength was 290 nm. The retention time was found to be 4.573 min for lornoxicam. The linearity of the method has been satisfied with Beer Lambert’s law in the concentration range of 5-25 µg/mL with a correlation coefficient of 0.9988. The mean recoveries assessed for lornoxicam were in the range of 100.39-101.86 %, indicating good accuracy of the method. The limit of detection and limit of quantification were found to be 0.03 and 0.11 µg/mL, respectively. The developed method has been statistically validated in accordance with ICH guidelines and found to be mass spectrometric compatible, simple, precise, and accurate with the prescribed values. Thus, the proposed method was successfully applied for the estimation of lornoxicam in routine quality control analysis of bulk, formulations and in dissolution samples.

RAPID AND SIMPLE DETERMINATION OF IBUPROFEN AND CAFFEINE IN FIXED-DOSE COMBINATION FORMULATIONS: APPLICATION TO DISSOLUTION STUDIES

Objective: To develop a UV-derivative spectrophotometric method with zero-crossing determinations for the simultaneous quantification of ibuprofen (IBU) and caffeine (CAF) in fixed-dose combination formulations (soft gelatin capsules). The proposed method was validated, and it was applied to determine the in vitro dissolution performance of IBU and CAF from a commercial formulation.&#x0D; Methods: The method is based on the use of the second-derivatives of the zero-order spectra and measurement at zero-crossing wavelengths. Linearity, accuracy, precision, stability, and influence of the filter were evaluated. Dissolution profiles of IBU and CAF were obtained with the USP Apparatus 2 at 100 rpm and 900 ml of 0.1 M phosphate buffer pH 7.4 as dissolution medium. Dissolution samples were treated with the proposed UV-derivative method and results were compared with data previously published.&#x0D; Results: The zero-crossing points for the determination of IBU and CAF were found at 235.6 nm and 218.8 nm, respectively. The method was linear in the range of 7.5-15 µg/ml for IBU and 5-25 µg/ml for CAF (R2&gt;0.999, *P&lt;0.05). The precision and accuracy of the method were within acceptable criteria (CV&lt;0.99% and recovery 97.97% for IBU and CV&lt;1.76% and recovery 99.05% for CAF). Fiberglass filters were the best option to filter samples and stability of all drugs was adequate when solutions were stored at 25 °C during 24 h. Dissolution of IBU and CAF at 60 min was 99-100% with dissolution profiles of sigmoidal S-shape. Weibull function and Logistic were the best-fit models that describe the in vitro dissolution performance of both drugs.&#x0D; Conclusion: The proposed UV-derivative method allows the simultaneous determination of IBU and CAF in fixed-dose combination formulations. The method generates reliable information that can be compared with published data. The proposed UV-derivative method is rapid and simple and can be easily adopted for routine analysis of IBU and CAF.

Outdoor dissolution and photodegradation of insensitive munitions formulations IMX-101 and IMX-104: Photolytic transformation pathway and mechanism study

New munition compounds have been developed to replace traditional explosives to prevent unintended detonations. However, insensitive munitions (IM) can leave large proportion of unexploded charge in the field, where it is subjected to photodegradation and dissolution in precipitation. The photolytic reactions occurring on the surfaces of IMX-101 and IMX-104 formulations and the subsequent fate of photolytic products in the environment were thoroughly investigated. The constituents of IMX-101 and IMX-104 formulations dissolve sequentially under rainfall in the order of aqueous solubility: 3-nitro-1,2,4-triazol-5-one (NTO) > nitroguanidine (NQ) > 2,4-dinitroanisole (DNAN) > 1,3,5-hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). A linear relationship between DNAN dissolution and rainwater volume was observed (r2: 0.86–0.99). It was estimated that it would take 16–228 years to completely dissolve these formulation particles under natural environmental conditions in Oracle, AZ. We used LC/MS/MS and GC/MS to examine the dissolution samples from IMX-101 and 104 particles exposed to rainfall and sunlight and found six DNAN photo-transformation products including 2-methoxy-5-nitrophenol, 4-methoxy-3-nitrophenol, 4-methoxy-3-nitroaniline, 2-methoxy-5-nitroaniline, 2,4-dinitrophenol, and methoxy-dinitrophenol, which are in good agreement with computational modeling results of bond strengths. The main DNAN photodegradation pathways are therefore proposed. Predicted eco-toxicity values suggested that the parent compound DNAN, methoxy-nitrophenols, methoxy-nitroanilines and the other two products (2,4-dinitrophenol and methoxy-dinitrophenol) would be harmful to fish and daphnid. Our study provides improved insight about the rain dissolution and photochemical behavior of IM formulations under natural conditions, which helps to form target-oriented strategies to mitigate explosive contamination in military training sites.

Development of 148Gd analysis method using stable Gd

The analytical method of Gd determination was developed with the aim to analyse 148Gd in environmental and bioassay samples. It involves the use of anion exchange resin, extraction chromatography, and cation exchange resin. Alkaline fusion and calcium oxalate co-precipitation are used for solid samples dissolution and liquid samples preconcentration, respectively. Total method recovery was tested with natural Gd (157Gd) using ICP-QQQ-MS. A maximum total recovery of 75 % was obtained.

Development and Validation of an Automated Zone Fluidics-Based Sensor for In Vitro Dissolution Studies of Captopril Using Total Error Concept.

In the present research, a zone fluidics-based automated sensor for the analysis of captopril in in vitro dissolution samples is reported. Captopril is reacted under flow conditions with Ni(II) (10 mmol L−1) in alkaline medium (0.15% v/v NH3) to form a stable derivate, which is monitored spectrophotometrically at 340 nm. The chemical and instrumental parameters were carefully investigated and optimized. The validation of the developed method was performed in the range of 5 to 120% of the expected maximum concentration using the accuracy profiles as a graphical decision-making tool. The β-expectation tolerance intervals did not exceed the acceptance criteria of ±10%, which means that 95% of future results will be encompassed in the defined bias limits. The variation of the relative bias ranged between −2.3% and 3.5% and the RSD values for repeatability and intermediate precision were lower than 2.3% in all cases. The limit of detection (LOD), and the lower and the upper limit of quantification (LLOQ, ULOQ) were satisfactory and found to be 1%, 5% and 120% (corresponding to 0.6, 2.78 and 66.67 μg mL−1 in dissolution medium). The developed method was successfully applied for the analysis of captopril in dissolution tests of two commercially available batches.