Stability indicating RP-HPLC method development and validation for quantification of impurities in gonadotropin-releasing hormone (Elagolix): Robustness study by quality by design.

The purpose of this research was to establish and validate a reverse phase HPLC method for the determination of Elagolix impurities in pharmaceutical dosage form. Mobile phase A, consisting of 10 mM sodium dihydrogen phosphate (pH 6.0) and acetonitrile in a 95:5 v/v ratio, and mobile phase B, containing 85:10:5 v/v/v of acetonitrile, Milli-Q water, and methanol, were used to achieve the method's specificity in the analytical column Kromasil 100-C18 (250 mm × 4.6 mm, 5 µm). The gradient program includes (%B/Time [min]: 36/0, 36/10, 38/15, 85/55, 85/65, 36/67, and 36/75). The flow rate is 0.8 mL/min. The overall run duration is 75.0 min, the injection volume is 10.0 µL, and the detection is at 210 nm in UV. The samples were subjected to hydrolysis, oxidation, and heat conditions in order to facilitate their forced degradation. The procedure was validated and determined with the standards of ICH guidelines. From the LOQ to a concentration level of 200%, the linearity of the technique was ascertained. An accuracy range of LOQ to 150% was established for the method, and the average recovery was acceptable. Design of experiments, part of the quality by design idea, was used to prove the method's reliability.

Quality by Design Tool Assessed Ultraperformance Liquid Chromatography Method for the Analysis of Remogliflozin and Teneligliptin in Oral Dosage Form.

The UPLC methodology was used to establish a method for determining the qualitative and quantitative content of teneligliptin and remogliflozin tablets in oral solid dose form, as no simultaneous method was available. The developed liquid chromatography method consists of an X-Bridge C18 100 mm × 3.5 mm, 2.1 mm column with an economical 0.2 mL/min flow rate. A wavelength of 248 nm was used for detection, and the temperature of the column compartment was 30 °C. The method was evaluated using a static tool quality by design after it was validated as per the regulations. The data from validation result in linearity for both analytes with a correlation coefficient of more than 0.999. The accuracy data were found from a minimum of 98.1 to a maximum of 100.9. All of the validation results met the acceptance criteria. The stability of the analytical solutions proved for 24 h at bench and refrigerator temperatures. Studies of force degradation proved the stability indicating the nature of the method. A factorial design was used to evaluate the method performance.

Quality by design tool-evaluated stability-indicating ultra-performance liquid chromatography method for the determination of drugs (ritonavir and darunavir) used to treat the human immunodeficiency virus/acquired immunodeficiency syndrome.

Ritonavir and darunavir were examined using a ultra-performance liquid chromatography (UPLC) approach in pharmaceutical dosage forms. The small number of analytical studies that are currently available do not demonstrate the method's stability or nature. The study sought to assess both chemicals using a stability-indicating approach with a relatively short run time. The HSS C18 (100 × 2.1 mm), 2-mm column was used for the chromatographic separation, and isocratic elution was used to achieve this. In the mobile phase, methanol and 0.01 M phosphate buffer (pH 4.0) were included in a 60:40 (v/v) ratio. Throughout the analysis, the flow rate was kept at 0.2 mL min-1 , and a photodiode array detector set to 266 nm was used to find the major components. The proposed method showed a linear response (r2  > 0.999), and the accuracy was between 98.0% and 102.0%. The precision data showed relative standard deviation ≤1.0%. The UPLC method for quantification of ritonavir and darunavir in pharmaceutical dosage forms using a very short run time of under a minute is the subject of the proposed article. To meet current regulatory criteria, the quality by design idea was used in the method performance verification.

Development and validation of apalutamide-related substances method in solid dosage forms using HPLC.

A related-substances method was developed for the anticancer drug formulation apalutamide 60 mg tablets and validated using a liquid chromatography gradient elution method. All of the impurities and degradants were separated using the Luna Omega 5 µm Polar C18 , (250 × 4.6) mm HPLC column with a 1.0 ml min-1 flow rate. The detection was done at 225 nm by injecting the 10 µl of injection volume, controlling the sample temperature at 10°C and maintaining the column compartment temperature at 30°C. The total run time was 85 min. A 0.01 m disodium phosphate dihydrate pH 4.20 ± 0.05 buffer mixed with acetonitrile in the ratio of 73:27 (v/v) was used as mobile phase A. Mobile phase B consisted of water and acetonitrile in the ratio 30:70 (v/v). The proposed method was validated as per the current regulatory guidelines. The method precisions (RSD) at 100% specification level were 1.41, 1.74, 1.84, and 1.66% for the four impurities. The accuracy results were obtained between 96.0 and 106.3% for the limit of quantitation to the 150% level. The standard and sample solutions stability were established for 44 h at 10°C. The correlation coefficient (r) value was >0.999 for all four impurities, indicating good linearity between the concentration and peak response: 0.9999, 0.9999, 0.9999 and 1.0000. These results show the method's linearity. The three filter compatibility was proved and it was concluded that 0.45 µm Nylon, PTFE and PVDF filters are suitable. The robustness of the method was established by varying the conditions. The method specificity was proved and the forced degradation data reveal the method's stability-indicating nature.