Trace level Determination of 2-(3-(trifluoromethyl)phenyl)propanal in Calcium Sensing Receptor drug by GCMS

Abstract

The study aimed to develop and validate the method for trace level analysis of 2-(3-(trifluoromethyl)phenyl)propanal (2-TFL) impurity in calcium sensing receptor drugs by gas chromatographic method using mass spectrometry (GC-MS). The method utilizes a capillary column with 6% cyanopropyl phenyl and 94% dimethylpolysiloxane stationary phase with EI source in Selective Ion Monitoring (SIM) mode under programming temperature was used. After successful development, the method was validated according to our in-house validation guidelines for trace level analysis. The method proved to be selective for 2-(3-(trifluoromethyl) phenyl)propanal impurity in drug substance. A dissolve and injection approach was adopted for sample introduction in a split mode. Methanol was used as a diluent. The calibration curves showed good linearity over the concentration range from 1.85 (LOQ to 5.56ppm (150%)) of the target concentration of 3 ppm. The correlation coefficient obtained was >0.999. A limit of detection (LOD) of about 0.56ppm was achieved and limit of quantitation (LOQ) of 1.85ppm was achieved for 2-(3-(trifluoromethyl)phenyl)propanal impurity, when the samples were prepared at 20mg/mL. While recovery proved to be 101.0% at Limit of quantification (LOQ) level, 102.1% at Target analytical level (TAL) and 98.1% at 150% of the TAL, demonstrate the absence of matrix effect.