A simple isocratic LC method for quantification of trace-level inorganic degradation impurities (ferricyanide,ferrocyanide, nitrite,and nitrate) in sodium nitroprusside injection and robustness by quality using design approach |
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Authors: | Parvateesam Yenda Naresh Kumar Katari Thirupathi Dongala Govind Vyas Lakshmi Narasimha Rao Katakam Santhosh Kumar Ettaboina |
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Institution: | 1. Analytical Research and Development, Slayback Pharma India LLP, Manjeera Trinity Corporate, JNTU, Hyderabad, India
Department of Chemistry, School of Science, GITAM Deemed to be University, Hyderabad, India;2. Department of Chemistry, School of Science, GITAM Deemed to be University, Hyderabad, India;3. Analytical Research and Development, Cambrex High Point Inc., High Point, NC, United States;4. R&D and Regulatory Compliance, Invahealth Inc., Cranbury, NJ, United States;5. Department of Chemistry, J. N. T. University, Hyderabad, India;6. Quality Control, Aurex Laboratories LLC, East Windsor, NJ, United States |
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Abstract: | This study developed and validated a trace-level quantification inorganic impurities method using reversed-phase HPLC and performed the robustness check using quality-by-design approach by varying the multiple factors simultaneously. This method is economical and simple and exhibits its stability-indicating nature for the determination of ferrocyanide (Fe(CN)₆]4–), ferricyanide (Fe(CN)6]3−), nitrate (NO3–), and nitrite (NO2–)] in sodium nitroprusside (SNP) drug substance and liquid dosage form. Chromatographic separation was achieved using a USP L43 column (ACE PFP, 150 × 4.6 mm, 3 μm) with a simple isocratic elution. The buffer consists of potassium dihydrogen phosphate (50 mM), tetrabutylammonium hydrogen sulfate (9 mM), and tetrabutylammonium hydroxide (25 mM). The buffer pH was adjusted to 7.2 with tetrabutylammonium hydroxide. The mobile phase was mixed with the buffer and acetonitrile (68:32 v/v). The flow rate was 0.8 mL/min, column temperature was maintained at 30°C, and injection volume was 5.0 μL. The SNP impurities were monitored at 225 nm using a UV detector. Further, the method was validated per the International Council for Harmonisation (ICH) guidelines, and forced degradation studies were carried out under different stress conditions. The detector responses were plotted against concentrations, and correlation was linear (r > 0.999) over the range of 0.8–7.5 μg/mL for ferricyanide; 1.0–37.5 μg/mL for SNP; and 0.2–7.5 μg/mL for ferrocyanide, nitrite, and nitrate. The method repeatability was established for all the impurities with relative standard deviation (%), and the results were found to be less than 2.0. |
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Keywords: | ferricyanide ferrocyanide nitrate nitrite RP-HPLC sodium nitroprusside |
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