title: Determination of the residual ethanol in hydroalcoholic sealed hard gelatin capsules by static headspace gas chromatography with immiscible binary solvents.
abstract: Static headspace gas chromatography (HS-GC) with immiscible binary solvents is described to quantitatively determine the residual ethanol used to seal the hard gelatin capsules by liquid encapsulated and microspray sealing (LEMS; cfs 1200, Greenwood, SC, USA). The effects of decane, dodecane, heptane, 0.1M HCl, N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidinone and dimethyl sulfoxide on the method sensitivity are compared. It is observed that the ethanol headspace concentrations can be increased by fourfolds when aliphatic hydrocarbon solvents are added into the aqueous sample solutions in a HS vial. In addition, a mathematic model based on the concentration equilibriums of liquid-liquid and liquid-gas phases is derived to quantitatively describe the ethanol headspace concentrations versus the volumes of the aliphatic hydrocarbon solvents. The proposed model fits well to the experimental data. The impacts of the oven temperatures and vial equilibration times on the ethanol headspace concentrations are also investigated. Furthermore, the potential interferences of the capsule placebo and hard gelatin capsule shells on the selectivity and quantitation of the method are discussed. The linearity is validated from 5 microg/mL to 500 microg/mL. The limit of quantitation is 5 microg/mL. The accuracy is determined to be 100.8+/-6%. Finally, this method is successfully used to determine the residual ethanol in the sealed capsules of 5mg and 10mg developmental Drug A, and 100mg and 200mg developmental Drug B.
authors.affiliation: Analytical Research and Development, Celgene Corporation, Summit, NJ 07091, USA. jli@celgene.com
authors.forename: Jingyi
authors.initials: J
authors.lastname: Li
authors.forename: Shan
authors.initials: S
authors.lastname: Shao
authors.forename: Mauro
authors.initials: M
authors.lastname: Solorzano
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Allmaier
authors.forename: Paul T
authors.initials: PT
authors.lastname: Kurtulik
mesh_terms: D000465:Algorithms; D002214:Capsules / Q000737:chemistry*; D002849:Chromatography, Gas / Q000379:methods*; D000431:Ethanol / Q000032:analysis* / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry*; D006838:Hydrocarbons / Q000737:chemistry*; D016014:Linear Models; D008962:Models, Theoretical; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013696:Temperature
chemical_list: D002214:Capsules; D006838:Hydrocarbons; D000431:Ethanol; D005780:Gelatin