Abstract

Mohan bhatale^1,2, Neelakandan kaliyaperumal², Gopalakrishnan Mannathusamy¹ and Gurunathan ramalingam¹

DOI : http://dx.doi.org/10.13005/ojc/370212

A simple, selective, precise and accurate Gas chromatographic method for determination of Triethyl orthoformate content (Genotoxic impurity) in 5-MIA is reported. The GC method development and validation as per the International Council for Harmonisation (ICH) guidelines Q2(R1). The effective chromatographic separations were achieved on DB-624, 60 m × 0.53 mm ID, with film thickness of 3.0 μm (Fused silica capillary column), Capillary injector temperature of 150°C, and Nitrogen Carrier gas. This method is unique as there is no UV response; hence GC Method was developed for Triethyl orthoformate. The elution was accomplished with the flow rate of 5.0 mL/min and Split Flow of 10 mL/minute. Detection was performed with FID detector (temp. 260°C) and with column oven temperature program. Methods range from limit of quantitation (LOQ) to 150% level with respect to specification concentration limit of impurity is linear and correlation coefficient of impurity is > 0.99. The linearity of Triethyl orthoformate covered from LOQ to 113 ppm (ie. LOQ to 150% of specification limit) and LOQ to 19 ppm wrt standard concentration. The limit of detection (LOD)values were observed were 2.5 ppm and limit of quantitation (LOQ) were 7.7 ppm, respectively. The parameters selected for the method validated were from international conference on harmonization guidelines, Indian pharmacopeia, USP. The percentage recovery from LOQ, 50% ,100% to 150% level of content were 87.70%, 98.60%, 102.25 and 96.59% respectively. The %RSD values were for LOQ to 150% were from 1.64%, 0.89%, 1.78 % and 1.49%. The range was covered from LOQ to 150% of standard concentration. The results of validation parameters were found in the acceptance range. Standard and sample were stable up to 30 h at when stored at room temperature. Also it was quite robust for the small change in method parameter like, change in column oven temperature
(± 5 degree). Hence from the above parameter it was concluded that the GC method with FID detector is selective, precise, linear, and robust for simultaneous estimation of Triethyl orthoformate in Drug Substances.

Triethyl orthoformate; GC-FID; Quantitative analysis; Genotoxic Impurity

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