Photolytic Degradation Research Articles

QbD-Driven Approach to Cleaning Method Development and Validation for Darunavir Analysis in Oral Films.

The current investigations involve developing a high-performance liquid chromatographic method that’s simple to operate, fast to establish, accurate, precise, and economical through design-enabled methods. A positive experimental design is offered to utilize the central composite design of pH and the mobile phase, two crucial components of the RP-HPLC technology. The chromatographic conditions were optimized with the release of Design Expert software version 13.0. Symmetry C18 column (4.6×150mm, 5µm) was used in the procedure, along with acetonitrile (20:80 v/v) and potassium dihydrogen orthophosphate buffer pH 4.0 as the mobile phase. There was a 0.70 ml/min flow rate. 263 nm is the wavelength of detection. Darunavir’s sharp, resolved peak was seen 2.3 minutes after swabbed samples from the 10*10 cm SS plate were injected. A linear calibration curve with an R2 of 0.9991 was observed in the concentration range of 0.25 to 25µg/ml. For precision %RSD is 1.03,1.48. Accuracy % concentration 50%,100%,150% mean recovery 99.43-100.53.LOD & LOQ 1.12µg/ml, 3.39µg/ml. Robustness was tested with modest modifications to the wavelength and flow rate. Forced degradation studies were carried out and found to be within the limits. the degradation parameters such as Acid, Base, Oxidative, Photolytic, and thermal degradation parameters are according to the ICH guidelines. % Assay was done for oral films and it was found to be within the limits. Thus, the outcomes unequivocally demonstrated that the QbD technique could be effectively used to enhance the HPLC method for the measurement of darunavir in production settings.

Study on hydrolytic, oxidative and photolytic degradation behaviour of anticancer drug sonidegib: Characterization of the products by UHPLC-Q-TOF-MS/MS, 2D NMR and in silico toxicity assessment

Sonidegib (SDG) is a USFDA-approved anticancer drug developed for treating basal cell carcinoma. The presented study is focused on forced degradation studies of SDG with special emphasis on oxidative and photolytic degradation. Stress testing was performed as per ICH guidelines in hydrolytic, oxidative, and photolytic stress, revealing the formation of 15 transformation products. The results demonstrated the sensitivity of SDG to photolytic exposure under UV-A light, as well as to oxidative stress conditions involving hydrogen peroxide and a radical initiator. The observed DPs are separated and identified using RP-LC-PDA using a linear gradient program equipped with C18 (4.6 ×250 mm, 5 µm) column. All the DPs with >0.1 % concentration are characterized using tandem mass spectrometry and DPs with complex, unstable and isomeric nature are enriched and studied using solution NMR. Enrichment studies unveiled the formation of DP-6, DP-11, DP-12 and DP-13 as major transformation products. Interpretation of characteristic fragments from MS/MS spectra, NMR chemical shifts, and NOEs are utilized to solve the structure of the DPs. Further elucidated structures are employed to propose the involved mechanisms in degradation pathway. In addition, the DPs are studied for toxicity in silico and the potential/plausible carcinogenic, genotoxic and mutagenic nature of the DPs are illustrated.

STABILITY INDICATING HIGH-PERFORMANCE THIN LAYER LIQUID CHROMATOGRAPHIC METHOD FOR EVEROLIMUS

Objective: Developing and validating a stability-indicating method for everolimus by HPTLC and depiction of degradation product of in alkaline conditions by LC-MS. Methods: The chromatographic separation was performed on aluminium plates pre-coated with silica gel 60 F254 as the stationary phase using Toluene: Methanol: Ethyl Acetate (6:2:2v/v/v) as the mobile phase. The evaluation was carried out at 277 nm. For the developed stability indicating method, the ICH Q2 (R1) guidelines were used for validation. Stress degradation studies like hydrolysis under different pH conditions, photolytic degradation, thermal degradation and oxidative degradation as per ICH Q1A (R2) and Q1B guidelines were performed. LC-MS analysis was carried out for the standard everolimus and its alkaline degradation sample using TOF analyser and the degradation pathway was proposed for each degradation product. Results: The Rf value of everolimus was found to be 0.63±0.03. The response was quite linear over the concentration range of 100-500 ng/band, with the regression coefficient value of 0.9921. Under alkaline hydrolytic conditions, everolimus was analyzed using Liquid Chromatography-Mass Spectrometry (LC-MS). The Retention Time (RT) and prominent mass fragmentation (m/z) for the everolimus standard were observed at 9.46 min with m/z values of 980.56 and 908.54. For the degradation products, DP-1 showed an RT of 8.88 min with m/z values of 349.23, 403.24, 574.33, and 646.35, while DP-2 exhibited an RT of 9.10 min with m/z values of 926.55, 614.32, and 542.30. These data were used to propose the structures of the degradation products. Conclusion: The proposed method can conveniently be applied for quantitative analysis of everolimus on routine basis and for stability testing under different stress environments.

Green Synthesis of Silver Nanoparticle Using Parmotrema parmutatum Extract and its Application in Colorimetric Sensing and Photolytic Degradation of Organic Dye

Background: Silver nanoparticles possess distinctive characteristics, including chemical stability, high thermal and electrical conductivity, and linear optical properties, making them unique and fascinating. The rise of green synthesis methods for silver nanoparticles is garnering significant interest among researchers, surpassing traditional chemical and physical approaches due to the environmentally friendly, cost-effective, and convenient nature of synthesis. This approach stands as a viable alternative across various sectors, encompassing research, industry, and environmental safety initiatives. Method: Parmotrema permutatum was utilized in the synthesis of silver nanoparticles, followed by their characterization using ultraviolet-visible spectroscopy, Fourier-transformed infrared spectroscopy, X-ray diffraction, energy dispersive X-ray analysis, and scanning electron microscopy. These nanoparticles are subsequiently employed for detecting methylene blue, formaldehyde, and hazardous mercury metal ions as well as photocatalytically degrading methylene blue. objective: Green Synthesis of Silver Nanoparticle Using Parmotrema parmutatum Extract and Its Application in Colorimetric Sensing Results: The silver nanoparticle synthesized was confirmed by a color change and the maximum peak of the SPR band was at 420 nm in the UV spectrum. The crystal has face-centered cubic (FCC) structure with an average size of 12.78 nm. The lichen extract contains polyphenolic groups which act as capping agents. synthesized silver nanoparticles were used to detect formaldehyde and hazardous Hg2+ ions separately. A color change was observed. The detection limit of Hg2+ was 600 μL. Likewise, silver nanoparticles were used to degrade methylene blue. The blue color of methylene blue disappeared. The efficiency of silver nanoparticles was found to be 72% in 4 hours and 87.82% in 24 hours. Conclusion: Parmotrema permutatum has the potential to reduce Ag2+ to Ago and acts as a capping and stabilizing agent, it can be used to biosynthesize silver nanoparticles and can detect formaldehyde, and Hg2+ ions, in addition, it also degrades methylene blue photolytically.

Photolytic Degradation of Water‐Soluble Organic Carbon in Snowmelts: Changes in Molecular Characteristics, Brown Carbon Chromophores, and Radiative Effects

AbstractWater‐soluble organic carbon (WSOC) deposited in ambient snowpack play key roles in regional carbon cycle and surface energy budget, but the impacts of photo‐induced processes on its optical and chemical properties are poorly understood yet. In this study, melted samples of the seasonal snow collected from northern Xinjiang, northwestern China, were exposed to ultraviolet (UV) radiation to investigate the photolytic transformations of WSOC. Molecular characteristics and chemical composition of WSOC and its brown carbon (BrC) constituents were investigated using high‐performance liquid chromatography interfaced with a photodiode array detector and a high‐resolution mass spectrometer. Upon illumination, formation of nitrogen‐ and sulfur‐containing species with high molecular weight was observed in snow samples influenced by soil‐ and plant‐derived organics. In contrast, the representative sample collected from remote region showed the lowest molecular diversity and photolytic reactivity among all samples, in which no identified BrC chromophores decomposed upon illumination. Approximately 65% of chromophores in urban samples endured UV irradiation. However, most of BrC composed of phenolic/lignin‐derived compounds and flavonoids disappeared in the illuminated samples containing WSOC from soil‐ and plant‐related sources. Effects of the photochemical degradation of WSOC on the potential modulation of snow albedo were estimated. Apparent half‐lives of WSOC estimated as albedo reduction in 300–400 nm indicated 0.1–0.4 atmospheric equivalent days, which are shorter than typical photolysis half‐lives of ambient biomass smoke aerosol. This study provides new insights into the roles of WSOC in snow photochemistry and snow surface energy balance.

Antibiotic Removal by Three Promising Microalgae Strains: Biotic, Abiotic Routes, and Response Mechanisms

Microalgae represent an alternative to conventional wastewater treatment, potentially improving antibiotic removal and offering a solution to combat the spread of antimicrobial resistance. Through batch assays, this study investigates the routes for antibiotic removal using three strains (Chlamydomonas acidophila, Auxhenochlorella protothecoides and Tetradesmus obliquus). Using mixtures of ciprofloxacin, clarithromycin, erythromycin, metronidazole, ofloxacin, sulfamethoxazole, and trimethoprim at concentrations simulating wastewater composition, it also assesses antibiotic effects on microalgae physiology. The three strains primarily removed antibiotics through rapid biosorption, achieving up to 91.5% removal for specific ones like ciprofloxacin. T. obliquus and C. acidophila showed efficacy, with total removals of 37.2% and 49.3%, respectively. Over time, A. protothecoides demonstrated the highest active removal efficiency, eliminating 22.1% of total antibiotics, with a notable 67.6% removal for sulfamethoxazole. Abiotic degradation through hydrolysis and photolysis contributed to ciprofloxacin, ofloxacin, clarithromycin, and erythromycin removal (34.7% to 96.7%), showing pH-dependent photolysis. However, algae induced a shading effect, reducing the photolytic and hydrolytic degradation of specific antibiotics. T. obliquus and C. acidophila were inhibited by antibiotics, whereas A. protothecoides showed a 30.6% growth rate increase. The stimulatory effect was also observed for the nutrient removal, with A. protothecoides showing a 46.6% increase in ammonium removal and a 44.8% increase in phosphate removal with antibiotics. Additionally, antioxidant activities remained stable, except for a notable increase in peroxidase activity for A. protothecoides and T. obliquus. The study confirms efficient antibiotic removal and stimulatory responses in the three algal strains, indicating their potential for wastewater treatment and combating antimicrobial resistance.

Analysis of omarigliptin forced degradation products by ultra-fast liquid chromatography, mass spectrometry, and in vitro toxicity assay.

Omarigliptin (OMG) is an antidiabetic drug indicated for the treatment of type 2 diabetes mellitus. Forced degradation studies are practical experiments to evaluate the stability of drugs and to establish degradation profiles. Herein, we present the investigation of the degradation products (DPs) of OMG formed under various stress conditions. OMG was subjected to hydrolytic (alkaline and acidic), oxidative, thermal, and photolytic forced degradation. A stability-indicating ultra-fast liquid chromatography method was applied to separate and quantify OMG and its DPs. Five DPs were adequately separated and detected in less than 6 min, while other published methods detected four DPs. MS was applied to identify and obtain information on the structural elucidation of the DPs. Three m/z DPs confirmed previously published research, and two novel DPs were described in this paper. The toxicity of OMG and its DPs were investigated for the first time using in vitro cytotoxicity assays, and the sample under oxidative conditions presented significant cytotoxicity. Based on the results from forced degradation studies, OMG was found to be labile to hydrolysis, oxidation, photolytic, and thermal stress conditions. The results of this study contribute to the quality control and stability profile of OMG.

Photolytic degradation of commonly used pesticides adsorbed on silica particles

The currently used pesticides are mostly semi-volatile organic compounds. As a result, a fraction of them can be adsorbed on atmospheric aerosol surface. Their atmospheric photolysis is poorly documented, and gaps persist in understanding their reactivity in the particle phase. Laboratory experiments were conducted to determine the photolysis rates of eight commonly used pesticides (i.e., cyprodinil, deltamethrin, difenoconazole, fipronil, oxadiazon, pendimethalin, permethrin, and tetraconazole) using a flow reactor. These pesticides were individually adsorbed on hydrophobic silica particles and exposed to a filtered xenon lamp to mimic atmospheric aerosols and sunlight irradiation, respectively.The estimated photolysis rate constants ranged from less than (3.4 ± 0.3) × 10−7 s−1 (permethrin; >47.2 days) to (3.8 ± 0.2) × 10−5 s−1 (Fipronil; 0.4 days), depending on the considered compound. Moreover, this study assessed the influence of pesticide mixtures on their photolysis rates, revealing that certain pesticides can act as photosensitizers, thereby enhancing the reactivity of permethrin and tetraconazole. This study underscores the importance of considering photolysis degradation when evaluating pesticide fate and reactivity, as it can be a predominant degradation pathway for some pesticides. This contributes to an enhanced understanding of their behavior in the atmosphere and their impact on air quality.

Stability‐Indicating HPLC Method Development and Validation for the Quantification of Tofacitinib Citrate and Its Related Substances Using Hydrophilic Liquid Interaction Chromatography

ABSTRACTA new stability‐indicating RPHPLC method with short run time has been developed and validated for tofacitinib citrate and its related substances. The novel HPLC method integrates hydrophilic interaction liquid chromatography (HILIC) technology as the stationary phase and employs a mobile phase composed of phosphate buffer (pH 7.0) and acetonitrile (45:55, %v/v) at a flow rate of 0.5 mL/min under isocratic elution. Analytes were monitored via a UV detector at 210 nm and with the column oven temperature at 30°C for a 20‐min analysis. Precision (%RSD) for Impurity‐A and Impurity‐B and tofacitinib met specifications at 2.4%, 0.8%, and 0.0%, respectively. Accuracy ranged from 86% to 100% for impurities, with LOD at 0.03% and LOQ at 0.05%–0.06%. Correlation coefficients exceeded 0.999 for impurities and tofacitinib citrate. Solution stability was confirmed for 24 h at room temperature. The method range was extended from LOQ to ∼1.5% for impurities and LOQ to ∼150% for tofacitinib citrate. The method's stability was evaluated under acid and base hydrolysis, oxidative and water hydrolysis, and thermal and photolytic degradation. Introducing HILIC as the stationary phase for this work proved effective, eliminating the need of ion pair reagents, reducing analysis time, and ensuring consistent results.

Analytical quality by design (AQbD) based optimization of RP-UPLC method for determination of nivolumab and relatlimab in bulk and pharmaceutical dosage forms

BackgroundThe Analytical Quality by Design (AQbD) methodology extends the application of Quality by Design (QbD) principles to the management of the analytical procedure life cycle, encompassing method creation, optimization, validation, and continuous improvement. AQbD assists in creating analytical procedures that are robust, reliable, precise, and cost-efficient. Opdualag™ is a combination of Nivolumab and Relatlimab, which are antibodies that block programmed death receptor-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) receptors, used to treat advanced melanoma. This work aims to develop and validate a reversed-phase ultra-performance liquid chromatography (RP-UPLC) method using AQbD principles to determine NLB and RTB in pharmaceutical products.ResultsA central composite design (CCD) comprising three factors arranged in five distinct levels was implemented via Design-expert® software to optimize the chromatographic conditions. A mathematical model was constructed and the effects of three independent factors namely flow rate (X1), percentage of methanol in the mobile phase (X2), and temperature (X3) on responses including retention time (Y1–2), resolution factor (Y3), theoretical plates (Y4–5), and tailing factor (Y6–7) were investigated. The software determined the optimal chromatographic conditions for the separation of NLB and RTB, which were as follows: 32.80% methanol in the mobile phase, 0.272 mL/min flow rate, 29.42 °C column temperature, and 260 nm UV detection. The retention time for NLB and RTB were 1.46 and 1.88 min, respectively. The method exhibited linearity across the concentration ranges of 4–24 µg/mL for RTB and 12–72 µg/mL for NLB. The limits of detection (LOD) and limit of quantification (LOQ) for NLB and RTB, respectively, were 0.89 µg/mL, 2.69 µg/mL and 0.15 µg/mL and 0.46 µg/mL. The percentage relative standard deviation (%RSD) of intraday and interday precision for NLB and RTB was below 2. The recovery percentages for NLB and RTB were determined to be 99.57–100.43% and 99.59–100.61%, respectively. Both drugs were found to be susceptible to oxidative and photolytic degradation in forced degradation studies.ConclusionsEmploying the AQbD-based methodology, a straightforward, fast, accurate, precise, specific, and stability-indicating RP-UPLC method has been established for the quantitative analysis of NLB and its RTB in pharmaceutical formulations.

Development and validation of stability indicating assay method for mitapivat: Identification of novel hydrolytic, photolytic, and oxidative forced degradation products employing quadrupole-time of flight mass spectrometry.

Mitapivat is a novel, first-in-class orally active pyruvate kinase activator approved by the US Food and Drug Administration in 2022 for the treatment of hemolytic anemia. There is no literature available regarding the identification of degradation impurities of mitapivat. The present study deals with the degradation behavior of mitapivat under various stress conditions such as hydrolytic, photolytic, thermal, and oxidative stress. The multivariate analysis found that the independent variables, that is, molarity, temperature, and time, are interacting with each other to affect the degradation of mitapivat. A specific, accurate, and precise high-performance liquid chromatographic (HPLC) method was developed to separate mitapivat from its degradation products. The separation was achieved on the C-18 column (250mm × 4.6mm × 5µm) using the combination of 0.1% formic acid buffer and acetonitrile in gradient elution profile. The method was validated as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use Q2(R2) guideline. LC-electrospray ionization-Quadrupole-time of flight was employed to identify degradation products. A total of seven novel degradation products of mitapivat were identified based on tandem mass spectrometry and accurate mass measurement. In-silico toxicity of mitapivat and its degradation products was qualitatively evaluated by the DEREK toxicity prediction tool.

Breaking barriers in pharmaceutical analysis: Streamlined UV spectrometric quantification and stability profiling of haloperidol and methylparaben in liquid formulations

This study aims to quantify haloperidol and methylparaben in a liquid pharmaceutical formulation (2 mg/ml) using UV spectrometry and the simultaneous equations method. Additionally, we explored the stability of haloperidol under various stress conditions. The UV analysis revealed maximum absorption peaks at 248 nm for haloperidol and 256 nm for methylparaben, using a 1 % (v/v) lactic acid solution as the solvent. Method validation, conducted according to ICH guidelines, affirmed the method's reliability, showing excellent results in terms of linearity, precision, accuracy, and sensitivity. The method allows direct application to finished products, enabling simultaneous quantification without extractions. Its simplicity, speed, and cost-effectiveness make it ideal for routine controls in pharmaceutical industry haloperidol solution analyses. The method extends to monitoring forced degradation, indicating photolytic and hydrolytic degradation under acidic and basic conditions, while affirming thermal and oxidative stability. This proposed UV spectrometric method serves as a compelling alternative to pharmacopeia-recommended techniques, simplifying simultaneous determination of the active ingredient and preservative. This streamlines analysis, reducing time and costs. Additionally, it proves valuable in small industries lacking sophisticated instrumentation, offering insights into active ingredient behavior during forced degradation.

An eco-friendly first and second derivative synchronous spectrofluorimetry for quantification of florfenicol in presence of its different degradation products. Application to kinetic stability study.

Two rapid, simple, sensitive and selective derivative spectrofluorimetric methods (first and second derivative synchronous spectrofluorimetric (FDSFS and SDSFS) procedures) have been developed for the analysis of florfenicol in the presence of its various degradation products. FDSFS was applied to assay the drug in the presence of its alkaline, oxidative and photolytic degradation products while SDSFS was used to quantify it in the presence of its acidic degradation product. These methods permitted quantification of florfenicol at corresponding λ Em of 288, 287, 279 and 284 nm without interferences from any of its degradation products. Full validation procedures were applied to the suggested method according to International Conference of Harmonization guidelines. Moreover, different degradation kinetic parameters were calculated such as half-life (t 1/2), degradation rate constant (K) and activation energy (E a). Using the analytical eco-scale, green analytical procedure index and analytical greenness metric approach AGREE as greenness assessment tools, the proposed method was found to be environmentally friendly.

Development and validation of stability-indicating method of etrasimod by HPLC/DAD/MS/MS technique with greenness profiling

Etrasimod, a novel selective sphingosine-1-phosphate receptor modulator, was recently approved by the U.S. Food and Drug Administration and the European Medicinal Agency for the treatment of moderately to severely active ulcerative colitis in adults. In this research, the forced degradation study as an integral part of drug product and packaging development, which generates data on degradation mechanisms, is published. The development and validation of the stability-indicating method using a superior high-performance liquid chromatography technique coupled with a diode array detector and tandem mass spectrometer was performed to support the forced degradation study and monitor the formation of degradation products. Etrasimod demonstrated good stability under elevated temperature and basic stress conditions, while acidic hydrolysis, oxidative, and photolytic degradation produced eight degradation products. The knowledge of degradation products will be useful in the long-term stability study for establishing the acceptance criteria of etrasimod as a drug substance and dosage form during quality control and stability assessment. The eco-friendliness of the developed forced degradation procedure was evaluated using various greenness appraisal tools. The green metric tools showed that the forced degradation procedure obeys eco-friendly conditions.

Development and Validation of Stability Indicating Liquid Chromatographic Method for Vandetanib: Application to Degradation Studies by LC-MS

Objective: The central goal of this research was to formulate and validate a stability-demonstrating assay approach using reverse-phase high-performance liquid chromatography (RP-HPLC) for the assessment of vandetanib, its primary degradation products, and their respective degradation pathways, which were identified and characterized using liquid chromatography-electrophore spray ionization-mass spectrometry (LC-ESI-MS).Methods: The method was designed and developed by employing a Grace C18 column (250 x 4.6 mm x4.0 μm) and deploying a mixture of methanol and 0.1% formic acid in H2O (in a proportion of 90:10, v/v) as the mobile phase, with a flow rate maintained at 1-mL/min. The analytes were detected at a wavelength of 249 nm. Additionally, vandetanib was subjected to various stress conditions, including acidic, alkaline, oxidative, thermal, and photolytic degradation, to unearth the degradation paths for the principal degradation products.Results: The approach was meticulously formulated and validated to ensure robustness, linearity, precision, accuracy, and linear regression analysis data. A high correlation coefficient of 0.9985 was obtained in the 2 to 12 μg/mL concentration range, demonstrating a robust linear relationship. Moreover, the limit of detection (LoD) and the limit of quantification (LoQ) were found to be 0.166 and 0.503 μg/mL, respectively. In the stress degradation studies, we noticed that vandetanib degraded in alkaline and acidic mediums. The liquid chromatography-mass spectrometry (LC-MS) technique was used to characterize the degradation products.Conclusion: The devised method demonstrated itself to be quick, sensitive, precise, accurate, and robust for the vandetanib analysis, thereby facilitating its routine testing.

Stability Indicating Force Degradation Study of Nintedanib in Bulk and Pharmaceutical Dosage Form

Assay of the nintedanib drug substance can be determined using a newly designed and verified reverse-phase high-performance liquid chromatography (RP-HPLC) method, even when degradation products from forced degradation experiments are present. By using gradient elution, the mobile phase was a mixture of 70% acetonitrile and 30% water by volume. Acid, base, peroxide, thermal, and photolytic degradation were among the stress conditions that the product was subjected to. During the thermal and photolytic breakdown processes, no extra contaminants were detected. Using validation criteria such as specificity, linearity, limit of quantitation (LoQ), accuracy, precision, robustness, and ruggedness, the developed technique was validated in accordance with International Council for Harmonization (ICH) recommendations. At a concentration of 12.4 ng/mL, the LoQ value was attained. The results showed good linearity (r2 > 1.00) across doses ranging from 2 to 10 μg/mL. Verification of recovery was done by adding concentrated solutions of 5, 10, and 15 μg/mL. So, newly developed RP-HPLC technology can separate Nintedanib from its main degradation products, and it can also estimate the drug substance’s concentration.

Thermodynamic and kinetic models for the photolytic and hydrolytic degradation of picaridin: A computational and theoretical study

The popularity of insect repellents presents the opportunity for continuous human and environmental exposure to such chemical mixtures. Consequently, the effects of their chemical components on human health and environmental safety is significantly reliant on their stability and hence, residence times under typical environmental conditions. Hence, for the first time, a thorough density functional theoretical (DFT) study on some possible hydrolytic and photolytic degradation pathways is presented and applied in the derivation of a comprehensive kinetic model, allowing evaluation of the residence time of picaridin; a very popular insect repellent. These results show that picaridin undergoes very slow hydrolysis via two pathways which present activation free energy barriers (ΔG‡) of ca. 225 and ca. 247 kJ mol−1 due to the asynchronous formation of four-membered cyclic activated complexes in both cases. Similarly, their photolytic transformations occur via two pathways, both of which are limited by the formation of the initial radical cation.

Liquid chromatography and liquid chromatography coupled with tandem mass spectrometry studies for the identification and characterization of degradation products of lobeglitazone

AbstractThe objective of the present research work was to demonstrate the application of liquid chromatography coupled with tandem mass spectrometry (LC‐MS/MS) for the separation, identification, and characterization of degradation products (DPs) of the drug lobeglitazone. The drug was subjected to various stress conditions such as oxidation, hydrolysis, thermal, and photolytic degradation as per the guidelines of the International Conference on Harmonization Q1A (R2). The drug was stable under thermal stress conditions, whereas it was susceptible to degradation in the other stress conditions forming four DPs. DPs were separated using a high‐performance LC system equipped with Zorbax SB C18 column (250 × 4.6 mm, 5 µm particles) using isocratic elution mode. The DPs were identified and characterized using MS and MS/MS. The chemical structure and fragmentation pattern were predicted for each degradant from the data obtained by mass studies. The drug and identified DPs were assessed by in‐silico approaches for predicting absorption, distribution, metabolism, and toxicity behavior. The in‐silico tools used for prediction were the pkCSM web server, ToxTree, and OSIRIS property explorer.

DEGRADATION ESTIMATION OF ROSUVASTATIN CALCIUM IN PHARMACEUTICAL TABLET FORMULATION

Objectives: The present objective was to undertaken the Rosuvastatin Calcium degradation in the tablets formulations with a rapid, economic, consistent, specific and simple analytical procedure. Methods: The analytical RP-HPLC was validated with mobile phase composition of methyl alcohol : cyanomethane : water (45:35:20,v/v). The detection was achieved with a flow 1.0 ml/min by using octylsilane column (250 x 4.6 mm, 5 µ), at 248 nm. Results: The established analytical procedure of Rosuvastatin Calcium was validated statistically for reproducibility, accuracy, specificity as per ICH-guideline. The correlation coefficient was 0.999 with the linearity concentration range 140-260 µg/ml. The percentage recovery was achieved 99.86 to 106.12 and RSD% of precision was 0.599. The specificity was confirmed by excellent photolytic and thermal stability of Rosuvastatin Calcium. The degradation statistical recovery of Rosuvastatin Calcium in dry, wet and thermal stage ware 99.25%, 99.52 % and 99.64% respectively validated. The developed peaks in the chromatograms of alkali, oxidation and acid decomposition of Rosuvastatin Calcium were confirmed by screening the degradation peaks and the recovery percentage were found 23.16 %, 85.59 % and 66.33 % respectively. Conclusions: The stress conditions of Rosuvastatin Calcium in degradation study is successfully developed and it is also important in stability to determined the highest lipid lowering agent in the body that block the manufacturing of cholesterol. The stress conditions like in aqueous acidic hydrolysis, oxidative, alkaline hydrolysis, thermal and photolytic degradation study was validated with a simple, cost efficient, linear, accurate, selective, specific, high performance liquid chromatography with a simple effortless mobile phase containing methyl alcohol, cyanomethane and water.

Development and Validation of Fast and Sensitive RP-HPLC Stability-Indicating Method for Quantification of Piroxicam in Bulk Drug.

A simple, rapid, sensitive, and cost-effective green solvent-assisted reverse-phase high-performance liquid chromatographic technique, coupled with a photodiode array detector, was developed and validated for the estimation of piroxicam (PRXM). The chromatographic separation was achieved by using a C-18 (250 × 4.6) mm, 5-μm stationary phase and a mobile phase consisting of methanol and 0.1% ortho-phosphoric acid in water in a ratio of (80:20) v/v at a flow rate of 1ml/min. The detection was carried out at a wavelength of 254nm with a constant injection volume of 10μL throughout the analysis. The calibration curve was observed to be linear over the optimum concentration range of 50-300μgmL-1, with an R2 value of 0.9995. The developed method was validated as per the International Council for Harmonisation (ICH) Q2 (R1) guideline. Various parameters like selectivity/specificity, accuracy/recovery, linearity, precision, detection limit, quantitation limit, robustness and stability of analyte in solution were performed for the method validation. The PRXM was evaluated under stressed conditions, including acidic, basic, oxidative, thermal and photolytic, as per ICH Q1 (R2) guidelines. Significant degradation was observed in acidic and basic degradation conditions. Conversely, the drug substance showed stability when exposed to oxidative, photolytic and thermal degradation conditions.