A Direct Standard Headspace Method for the Determination of Chloroacetic Acid and Dichloroacetic Acid in Armodafinil Drug Substance by GC-MS. Issue 1 (2nd January 2022) - Venkata Ramana Reddy, Junuthula
Abstract: A selective GC-MS method was developed and evaluated for the determination of genotoxic impurities Chloroacetic acid (Cl-AcOH) and Dichloroacetic acid (DCl-AcOH) in Armodafinil ( AMD) drug substance. Chromatographic separation of Cl-AcOH and DCl-AcOH was achieved on DB-624 column (30 m x 0.32 mm, 1.8 µm), which contains 6% cyanopropylphenyl and 94% dimethylpolysiloxane stationary phase by helium carrier gas. Mass fragment m/z 59 was selected for the quantification of both Cl-AcOH and DCl-AcOH impurities. Further, mass fragments m/z=108 was selected for Cl-AcOH and m/z=83 was selected for DCl-AcOH as qualifier ion. The performance of the method was assessed by evaluating the specificity, linearity, sensitivity, precision and accuracy experiments. The limits of detection (LOD) and limits of quantification (LOQ) values for Cl-AcOH were 0.00003 µg mL −1, 0.00009 µg mL −1 and for DCl-AcOH analyte were 0.00003 µg mL −1 and 0.00009 µg mL −1 respectively. The correlation coefficient values of linearity experiment were 0.9929 for Cl-AcOH, 0.9908 for DCl-AcOH. The average recovery for Cl-AcOH was in the range of 104.7% to 111.4% and for DCl-AcOH was in the range of 108.2% to 111.7%. The results proved that the method is suitable for the determination of Cl-AcOH and DCl-AcOH contents in Armodafinil drug substance and method can be successfully applied in the quality control analysis. GRAPHICAL ABSTRACT: UF0001