Application of the high-resolution HPLC–MS/MS method for identification and quantitative determination of impurities in the substance of the drug «Lomustine»

Due to the state program of the Russian Federation "Development of the pharmaceutical and medical industry" (Pharma-2020), extended until 2024, the interest in the possibility of organizing the production and quality control of imported medicinal substances directly on the territory of the Russian Federation has significantly increased. In this case, the drugs included in the lists of "Indispensible and essential drugs" and "Provision of necessary drugs" [1] are of particular importance. One of the drugs often used in the chemotherapy of malignant tumors is the drug "Lomustine", which includes 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea as an active ingredient [1-3].

HPLC Tests in Quality Control under the Market Surveillance Program for Medicinal Products Containing Amlodipine and Valsartan

Background: Quality is one of the three main characteristics of medicinal products. The quality assurance process is multi-stage: during the manufacturing, quality control is the commitment of the manufacturer, but after medicinal products become part of the distribution and pharmacy network, analytical quality control is carried out within the program for Market Surveillance. There are different approaches in conducting quality control of medicinal products under the Market Surveillance Program. Aim: The aim of the study is to compare the results obtained under two approaches: individual testing and testing by groups with the same active substance. Methods: In this study, comparative tests for assay and purity were carried out within two groups of medicinal products from the antihypertensive group containing Amlodipine besilate and Valsartan. Analyses were performed in accordance with the available pharmacopoeial monographs, as well as those from literature sources. Results: The results from the assay tests show a significant difference in the same product tested. Analytical methods for the determination of impurities also show different results when analyzing the same medicinal product. Conclusion: Considering the performed analytical tests, the obtained results can be used to make several conclusions and suggestions concerning the optimisation of the Annual Market Surveillance Program

Development and validation of RP-UPLC method for the determination of betamethasone dipropionate impurities in topical formulations using multivariate central composite design approach.

Current study portrays a specific, accurate, simple and rapid UPLC method development for the determination of impurities present in two different topical formulations (Cream and Ointment) of betamethasone dipropionate. The...

HPLC method for simultaneous determination of impurities and degradation products in Cardiazol

Aim. The aim of study was to develop a simple and accurate procedure that could be applied for the determination of impurities and degradation products in cardiazol. Materials and methods. Separation in samples was carried out with Acquity H-class UPLC system (Waters, Milford, USA) equipped with Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm) (Waters, Milford, USA). Xevo TQD triple quadrupole mass spectrometer detector (Waters Millford, USA) was used to obtain MS/MS data. Mobile phase A: 0.1% solution of trifluoroacetic acid R in water R; Mobile phase B: acetonitrile R. Samples were chromatographed in gradient mode (Table 1). Flow rate of the mobile phase: 1 ml / min. Column temperature: 30 °С. Detection: at 240 nm wavelength. Injection volume: 10 μl. Results. The retention time of the main substance is about 18.5 minutes. The order of the peak, the retention times and relative retention times: impurity B (12.04, 0.65); impurity А (18.5; 0.98); Cardiazol (18.87; 1.00). The LOD and LOQ values obtained were in the range of 30 ng/mL to 100 ng/mL and 80 ng/mL to 310 ng/mL respectively (with respect to sample concentration of 2 mg/ml). Linearity was established in the range of LOQ level to 0.2% having regression coefficients in the range of 0.9996 to 0.9999. The change in the temperature of the column affects the degree of separation of cardiazol and the impurity A, and thus, with a decrease of 5 ° C, the degree of separation is (1.06), while with increasing this index (3.43). When changing the flow rate of the mobile phase, the degree of separation changes in the following order, with a decrease to 0.9 ml / min separation (1.90), with an increase in speed to 1.1 ml / min (2.45). When the number of mobile phase B decreases by 5%, the degree of separation varies by (2.65), with an increase of 5% (1.82). In comparison with the chromatogram of the tested solution, the substance is not resistant to the action of peroxide, alkaline and acid decomposition. Conclusion. 1) HPLC method was developed and validated for the simultaneous detection and quantitation of impurities formed during the synthesis of cardiazol. 2) The method proved to be sensitive, selective, precise, linear, accurate and stability-indicating.