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RATIONALE: Nirmatrelvir is a protease inhibitor that is essential for virus replication. Nirmatrelvir is indicated for the management of mild to severe cases of COVID-19 in individuals who are 12 years of age or older. Forced degradation studies of nirmatrelvir were carried out on the drug substance in solid and solution forms, subjecting it to various stress conditions according to International Conference on Harmonisation (ICH) Q1A(R2) and Q1B guidelines. The analytical method was validated as per the ICH Q2(R1) guidelines. METHODS: The drug substance (nirmatrelvir) was subjected to hydrolysis (acidic, alkaline, and neutral), thermal, photolytic, and oxidative stress conditions. Five degradation products (DPs) of nirmatrelvir formed under hydrolytic (acidic and alkaline) and oxidative (2,2-azobisisobutyronitrile) stress conditions. These degradation products were identified and separated using reverse-phase HPLC on a phenomenex kinetex C8 column (250 mm × 4.6 mm × 5 µm) with gradient elution. The mobile phase consisted of 0.1% formic acid and acetonitrile, and detection was carried out at a wavelength of 210 nm. RESULTS AND CONCLUSIONS: Nirmatrelvir and its five DPs were efficiently separated using reverse phase-HPLC. These five DPs were identified and characterized using LC-electrospray ionization (ESI)-Q-TOF-coupled mass spectrometry analysis in the ESI-positive ionization mode. The formation mechanisms of the DPs and the most probable mass fragmentation pathways for both nirmatrelvir and its DPs were elucidated. The developed method demonstrated selectivity, accuracy, linearity, and reproducibility, making it appropriate for quality control of nirmatrelvir and future research studies. Additionally, the physicochemical and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of nirmatrelvir and its DPs were predicted using ADMET predictor software. The toxicity profile revealed that DP2 and DP3 have teratogenic effects while DP1 and DP3 caused phospholipidosis.

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Objectives: The primary goal of this study was to create and validate a simple, precise, sensitive, and accurate ultra-performance liquid chromatography (UPLC) method for estimating tirbanibulin in pure and dosage form. Materials and Methods: A UPLC technique was developed using a Waters Acquity UPLC Phenyl (100 x 2.1 mm, 1.7 µm) column. The developed technique was validated in accordance with the International Conference on Harmonization (ICH) guidelines. Results: Tirbanibulin was separated chromatographically with high resolution using the mobile phase acetonitrile: buffer (30:70 v/v) at 0.5 mL/min, 5 µL injection volume, and 220 nm wavelength. The validated technique was found to be linear in the 1-15 µg/mL range. The detection and quantification limits for tirbanibulin were 0.03 and 0.1 µg/mL, respectively. The percentage relative standard deviation was less than 2%, demonstrating the precision of the developed technique. Furthermore, the recovery rate was nearly 100%, confirming the accuracy of the method. Minor modifications to the chromatographic conditions demonstrated the robustness of the method. Conclusion: The developed analytical method was precise, simple, reproducible, and sensitive. Consequently, it can be used to determine tirbanibulin.

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Margetuximab was approved for the treatment of advanced HER2+ breast cancer. A feasible analytical technique that can measure this drug was obligatory. In light of this, a novel and thoroughly validated liquid chromatographic (LC)-tandem mass spectrometric (MS/MS) approach was developed for the quantification of margetuximab in rat plasma. The liquid-liquid extraction method was used to extract the analyte from rat plasma. The analyte was separated using acetonitrile and formic acid buffer (30:70) as a mobile phase on Waters, alliance e-2695 model HPLC having Symmetry C18 column, 150 mm × 4.6 mm, 3.5-µm column. The overall runtime was 6 min at a flow rate of 1.0 ml/min. The method showed significant sensitivity and acceptable linearity over the concentration range of 6-120 ng/ml. Accuracy was within 98.51-99.92%. The intraday precision ranged between 0.41 and 8.98% CV. Also, the findings of pharmacokinetic parameters such as Cmax, tmax, AUC0-∞, AUC0-t, and half-life results of margetuximab showed that the technique was helpful for accurately measuring drug concentrations in rat plasma. The method that was developed was useful and effective for quantifying margetuximab.

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RATIONALE: Ozenoxacin (OXC) is an antibiotic used topically to treat impetigo. This study aimed to evaluate the degradation products (DP) of OXC drug substance under different stress conditions, including hydrolysis, oxidation, thermal and photolysis, in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines Q1A(R2) and Q1B. The analytical technique was validated in compliance with ICH Q2(R1) requirements. METHODS: The drug substance underwent degradation under various forced degradation conditions, including thermal, oxidative, photolytic and hydrolytic (neutral, acidic and basic) degradation. Overall, four DPs were formed under oxidative stress conditions with AIBN. The formed DPs were identified and separated using a Shimadzu LC system with a reversed-phase Phenomenex Kinetex C18 column (4.6 × 250 mm, 5 µm), using 10 mM NH4 CH3 COOH buffer (pH -5.0) as mobile phase A and acetonitrile as mobile phase B at a detection wavelength of 254 nm. RESULTS AND CONCLUSION: The drug was found to be stable in neutral, acidic, basic and oxidative degradation conditions with hydrogen peroxide. Liquid chromatography-electrospray ionisation-quadrupole time-of-flight-tandem mass spectrometry- was employed in positive ionisation mode to analyse both the drug and the mass of the identified DP. The mechanism and the pathway of mass fragmentation have been proposed. The developed method was accurate, repeatable, linear and selective for further research. The ADMET Predictor software was applied to predict the in silico toxicity of the drugs and its DPs as well as their physicochemical characteristics.

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Rationale: A simple, sensitive, reliable, validated, inductively coupled plasma mass spectrometric method for the determination of aluminium and magnesium using a simple common microwave-assisted digestion sample preparation technique for a few commonly used formulations was developed and validated according to International Conference on Harmonization Q3D and the United States Pharmacopeia general chapter <232> and <233>. The following pharmaceutical dosage forms were considered for estimation of aluminium and magnesium: Alumina, magnesia simethicone oral suspension, Alumina, magnesia simethicone chewable tablets, alumina and magnesia oral suspension, alumina and magnesium carbonate oral suspension. Methods: The methodology included optimizing a common microwave assisted digestion method, selecting the isotopes, choosing the measurement technique, and designating internal standards. The finalized microwave assisted procedure was a two-step program where in the first step the samples were ramped for 10 min to a temperature of 180 °C and hold for 5 min followed by ramping for 10 min to a temperature of 200 °C and hold for 10 min. Magnesium (24Mg) and aluminium (27Al) isotopes were finalized, internal standard assigned for both the isotopes was yttrium (89Y) with Helium (kinetic energy discrimination-KED) as the measuring mode. System suitability was run before initiating analysis to ensure that system performance was consistent. Results: Analytical validation parameters like specificity, linearity (from 25% to 200% of sample concentration), the detection limit and the limit of quantification were established. For all these dosage forms, the method's precision was demonstrated by analyzing the percentage relative standard deviation for six injections. Accuracy was established from 50% to 150% of instrument working concentration (J-levels) for aluminium and magnesium for all the formulations and was found to be within the range of 90-120%. Conclusion: This common analysis method, along with the common microwave-digestion technique applies to numerous types of matrices for a finished dosage form with aluminium and magnesium.

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Atorvastatin calcium is employed as front-line treatment for cardiovascular diseases. According to the international conference on harmonization (ICH) guideline ICH Q3D, elemental impurities can come into drug products from various sources. These elemental impurities do not have any therapeutic benefit to the end-user. On the contrary, it harms the normal physiological system. Class 1 elements like arsenic, cadmium, mercury, and lead are inorganic impurities that can cause toxic effects on the human body. Nickel was used as a catalyst during the synthesis process of atorvastatin calcium. It comes under the Class-2A, can cause toxicity to humans, and must be quantified. A simple, fast, reliable inductively coupled plasma mass spectrometric method for the estimation of elemental impurities like arsenic, cadmium, mercury, lead, and nickel in atorvastatin calcium by open sample digestion technique was developed and validated in accordance with ICH Q3D and USP < 232 > and USP <233 > general chapter. Internal standards like indium, terbium, thallium, bismuth and yttrium were used to correct the non-spectral interferences that were generated during analysis. Gold was added to all solutions as it preserves mercury by amalgamation. The system performance was evaluated every time my performing system suitability parameters. The limits for all the elements were fixed in accordance with ICH Q3D. The limit of detection and the limit of quantification for all the five elements were estimated. Method specificity was proven by checking for interferences due to the sample matrix and other elements. Linearity of each element in standards was established from 25% to 200% of sample concentration, and correlation coefficients were found to be not less than 0.999. The accuracy of the method was demonstrated at three spiking levels at 50%, 100%, and 150% of the J-value for all the elements. The recoveries for all elements at each level were within the range of 90-120%. Method precision was proved at 100% J-value. The relative standard deviation of all elements was less than 5%. It concludes that this newly developed and validated reliable inductively coupled plasma mass spectrometric method for estimating of elemental impurities like arsenic, cadmium, mercury, lead, and nickel in atorvastatin calcium was within the permitted limit and suitable for routine use.

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Objective: To evaluate the mosquito larvicidal activity of Pongamia pinnata (P. pinnata) extracts against three mosquito vectors.Methods:The larval mortality was found in both methanol and hydroalcohol extracts of P. pinnata against fourth instar larvae of Culex quinquefasciatus, Aedes aegypti and Anopheles stephensi. The mortality was observed 24 h and 48 h after treatment, data was subjected to probit analysis to determine lethal concentration (LC50 and LC90) to kill 50 and 90 percent of treated larvae of tested species.Results:The methanol and hydroalcohol extracts of bark part of P. pinnata L were tested against Culex quinquefasciatus, Aedes aegypti and Anopheles stephensi with LC50 values of 84.8, 118.2 and 151.7 ppm; 97.7, 128.3 and 513 ppm. The highest larval mortality was found in methanol extract of P. pinnata when comparable to the hydroalcohol extract.Conclusions:These results suggest that both methanol and hyrdoalcohol extracts have the potential to be used as an ideal ecofriendly approach for the control of disease vectors. This could lead to isolation of novel natural larvicidal compounds.

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In the present study, a series of novel Schiff bases of isatin [5a-5l] were synthesized by condensation of imesatin with different aromatic aldehydes. The imesatins were synthesized by the reaction of isatin with p-phenylenediamine. The chemical structures of the synthesized compounds were confirmed by means of Infrared (IR), Mass spectroscopy, and Elemental analysis. These compounds were screened for the analgesic activity by the tail-immersion method at a dose of 200 mg/kg body weight. Among the tested compounds 3-(4-(4-hydroxy-3-methoxylbenzylideneamino) phenylimino) indoline-2-one (5i) exhibited better analgesic activity when compared to standard pentazocine. From the above-mentioned results it may be concluded that compounds containing electron-donating groups exhibit better analgesic activity than the electron-withdrawing groups.

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BACKGROUND: Recent investigations have shown that the antioxidant properties of plants could be correlated with oxidative stress defense and different human diseases. In this respect flavonoids and other polyphenolic compounds have gained the greatest attention. The plant Cytisus scoparius contains the main constituent of flavone and flavonals. The present study was undertaken to evaluate the in vitro antioxidant activities of extract of aerial part of Cytisus scoparius. METHODS: The plant extract was tested for DPPH (1, 1-diphenyl, 2-picryl hydrazyl) radical scavenging, nitric oxide radical scavenging, superoxide anion radical scavenging, hydroxyl radical scavenging, antilipid peroxidation assay, reducing power and total phenol content. RESULTS: The extract exhibited scavenging potential with IC50 value of 1.5 microg/ml, 116.0 microg/ml and 4.7 microg/ml for DPPH, nitric oxide and superoxide anion radicals. The values were found to lesser than those of vitamin C, rutin, and curcumin, as standards. The extract showed 50% protection at the dose of 104.0 microg/ml in lipid peroxidation induced by Fe2+/ ascorbate system in rat liver microsomal preparation. There is decrease in hydroxyl radical generation with IC50 value of 27.0 microg/ml when compared with standard vitamin E. The reducing power of the extract depends on the amount of extract. A significant amount of polyphenols could be detected by the equivalent to 0.0589 microg of pyrocatechol from 1 mg of extract. CONCLUSION: The results obtained in the present study indicate that hydro alcoholic extract of aerial part of Cytisus scoparius is a potential source of natural antioxidants.

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