A SENSITIVE HEADSPACE METHOD FOR THE DETERMINATION OF 2-BROMOPROPIONIC ACID AND 2-BROMOPROPIONYL CHLORIDE IN TIOPRONIN DRUG SUBSTANCE BY GC-MS
Junuthula Venkata Ramana Reddy*, Manabolu Surya Surendra Babu, Masani Narendra Kumar and Hemant Kumar Sharma
ABSTRACT
A selective GC-MS method was developed and evaluated for the determination of genotoxic impurities namely, 2-Bromopropionic acid (Br-PrOH) and 2-Bromopropionyl chloride (Br-PrCl) in Tiopronin (TPN) drug substance. The background of the method involves derivatization process, in this process, both analytes (Br-PrOH and Br-PrCl) are converted into Methyl 2-Bromopropionate with methanol in the presence of sulfuric acid and both analytes quantified as Methyl 2-Bromopropionate. Chromatographic separation was achieved on Zebron ZB-624 column (30 m x 0.32 mm, 1.8 μm), that contains 6% of cyanopropylphenyl and 94% of dimethylpolysiloxane as stationary phase by passing helium as carrier gas. Mass fragment m/z-107 was selected as quantification ion and m/z-87 was selected as qualifier ion for the determination of Methyl 2-Bromopropionate. The performance of the method was assessed by evaluating the specificity, linearity, sensitivity, precision and accuracy experiments. The method was specific and precise for 2-Bromopropionic acid and 2-Bromopropionyl chloride including other mass fragments exits from Tiopronin. The limit of detection (LOD) and limit of quantification (LOQ) values for Methyl 2-Bromopropionate was 0.004 μg mL-1 and 0.012 μg mL-1 respectively. The correlation co-efficient value for linearity experiment was 0.9992. The average recovery was in the range of 97.0% to 102.9%. The results proved that the method is suitable for the determination of Br-PrOH and Br-PrCl contents as Methyl 2-Bromopropionate in Tiopronin drug substance and method can be successfully applied for the quality control analysis.
Keywords: Gas chromatography, Tiopronin, Genotoxicity, Derivatization, Quantification.
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