Abstract
Objective: To develop and validate new, simple and rapid analytical method for determination of related impurities in isosulfan blue drug substances by the liquid chromatographic method as per ICH guidelines.Methods: The chromatographic separation obtained between drug substance i.e. isosulfan blue and its related impurities (Impurity-A, Impurity-B and Impurity-C) on C18 (100 x 2.00 mm) 1.9µ UPLC column using a mobile phase system containing 0.1 % perchloric acid in water (Mobile phase A) and 0.1 % perchloric acid in mixture of 30 volumes of water and 70 volumes of acetonitrile (Mobile Phase B) with gradient program; detector wavelength 220 nm and column temperature 30 °C. The developed method was extensively validated according to ICH guidelines.Results: Good linearity was observed for isosulfan blue, impurity-A, impurity-B and impurity-C, linearity was calculated from loq Level To 150%with respect to specification level. The correlation coefficient R = 0.999 was proved and showed that the method is robust. The limit of detection of isosulfan blue, impurity-A, impurity-B and impurity-C were found to be 0.010%, 0.015%, 0.030% and 0.0075 % respectively and limit of quantitation of isosulfan blue, impurity-A, impurity-B and impurity-C were found to be 0.030%, 0.030%, 0.045% and 0.015% respectively for 2ml injection volume. The percentage recovery of isosulfan blue and its related impurities were ranged from 94.0 to 108.0 in bulk drug samples. Isosulfan blue sample solution and mobile phase were found to be stable for at least 72 h. The proposed method was found to be suitable and accurate for the quantitative determination of impurity-A, impurity-B, impurity-C and other unknown impurities in isosulfan blue drug substances.Conclusion: A new, simple and rapid method has been developed and validated for separation and determination of impurity-A, impurity-B, impurity-C and unknown impurities of isosulfan blue by the reverse-phase liquid chromatographic method. Analytical method was developed and validated as per ICH guidelines.The developed method can be used for the quantitative determination of impurity A, impurity B, impurity C and unknown impurities in isosulfan blue drug substances in pharmaceutical industry.
Highlights
Isosulfan blue, having a chemical name, N-[4-[[4-(diethylamino) phenyl](2,5-sulfophenyl) methylene]-2,5-cyclohexadien-1-ylidene]N-ethylethanaminium,sodium salt [1]
The developed method can be used for the quantitative determination of impurity A, impurity B, impurity C and unknown impurities in isosulfan blue drug substances in pharmaceutical industry
AR grade perchloric acid purchased from JT baker, HPLC grade acetonitrile purchased from biosol, AR grade sodium dihydrogen phosphate dihydrate purchased from Merck and Millipore water is used for mobile phase preparation and diluent preparation
Summary
Isosulfan blue, having a chemical name, N-[4-[[4-(diethylamino) phenyl](2,5-sulfophenyl) methylene]-2,5-cyclohexadien-1-ylidene]N-ethylethanaminium,sodium salt [1]. The chemical formula is C27H31N2NaO6S2; chemical structures show in The chemical structure has been obtained from a process for the preparation of isosulfan blue,” U. Impurity-A (Des ethyl analogue) is a process related impurity, may arise during the manufacturing process of ISO-IV. During oxidation of ISO-III this impurity formation is possible, the chemical structure shown in Impurity-B (patent blue) is process related impurity. This impurity is patent blue, which is isomeric impurity of isosulfan blue, chemical structure show in This is carryover impurity of ISO-III and may arise during the manufacturing process of Isosulfan blue, chemical structure show in This is carryover impurity of ISO-III and may arise during the manufacturing process of Isosulfan blue, chemical structure show in (fig. 4)
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