Trace analysis of residual methyl methanesulfonate, ethyl methanesulfonate and isopropyl methanesulfonate in pharmaceuticals by capillary gas chromatography with flame ionization detection.
A capillary gas chromatographic method using flame ionization detection was developed and validated for the trace analysis (ppm level) of methyl methanesulfonate, ethyl methanesulfonate, and isopropyl methanesulfonate in pharmaceutical drug substance. The method utilizes a megabore capillary column with bonded and crosslinked polyethylene glycol stationary phase. A dissolve-and-injection approach was adopted for sample introduction in a splitless mode. The investigated sample solvents include acetonitrile, ethyl acetate, methylene chloride, 1,2-dichloromethane, and toluene. Aqueous mixtures of acetonitrile and water can also be used as sample solvent. A limit of detection of about 1 microg/g (1 ppm) and limit of quantitation of 5 microg/g (5 ppm) were achieved for the mesylate esters in drug substance samples. The method optimization and validation are also discussed in this paper.
Li
Weiyong
W
Global Analytical Development, Johnson and Johnson Pharmaceutical Research and Development, LLC, Raritan, NJ 08869, USA. wli1@prdus.jnj.com
D002849:Chromatography, Gas / Q000379:methods*; D005020:Ethyl Methanesulfonate / Q000032:analysis*; D008698:Mesylates / Q000032:analysis*; D008741:Methyl Methanesulfonate / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D008698:Mesylates; D004364:Pharmaceutical Preparations; D005020:Ethyl Methanesulfonate; D008741:Methyl Methanesulfonate; C002531:isopropylmethanesulfonate