Development and Validation of Analytical Method for Estimation of Residual Solvents in Dabigatran Etexilate Mesylate Pellets Using Gas Chromatography

Abstract

Introduction: A simple, sensitive, accurate and specific method on head space gas chromatography (GC-HSS) was developed and validated for the estimation of residual solvents of (IPA & DCM) in Dabigatran pellets of finished product, which is a categories of oral anti coagulation drug that acts as direct thrombin (factor II a) inhibitor. It is anticoagulant activity used for prevention of clots and embolism after surgery of hip or knee replacement.

Result: Identification and quantification of residual solvents in processing of pellets were achieved on Agilent DB-624 column have dimensions of 30 m long ,0.53 mm/ min, coated with 3.0 μm cross linked. Carrier gas as commonly nitrogen are used. Linear velocity of carrier are 35cm/sec, then column temperature initially 35⁰C then increase 260⁰C at rate of 35⁰C/min to maintain next 16 min. These developed method was validated as per ICH guideline and found to no interference due to blank and placebo in standard and sample solutions. Linearity range were solvents of dabigatran as IPA is 8.25 ppm to 75 ppm and DCM between 1.21 to 9 ppm. Sensitivity of dabigatran to estimated solvents were LOD of IPA 7.7 and LOQ of 23.5 and DCM of LOD 8.0 and LOQ of 23.8 was S/N ratio evaluted. % recovery was IPA & DCM were calculated between 92.6% to 105.6% and 92.9% to 106.5 %. % RSD for precision of solvents were found 1.4% and 1.3%.

Conclusion: The developed unique method can be very well employed and to monitor and control limit of residue of Isopropyl alcohol (IPA) and Dichloromethane (DCM) in dabigatran pellets (API).