title: High-speed gas chromatographic analysis of solvents in pharmaceuticals using solid phase microextraction.
abstract: A simple, inexpensive and rapid analytical approach for the determination of organic volatile impurities in pharmaceutical drug substances is developed, where sample preparation step was conducted using solid phase microextraction (SPME), followed by a fast GC separation. With an extraction time between 3 and 5 min and separation of 13 solvents in less than 3 min employing fast temperature programming using resistively heated column, organic volatile impurities can be analyzed within a total analysis time of 6-9 min. Various SPME phases were evaluated towards sensitivity and selectivity for the extraction of 13 commonly found solvents in drug substances dissolved in dimethyl sulfoxide and water. A 2-cm Carboxen/polydimethyl siloxane/divinylbenzene (Carboxen/PDMS/DVB) phase and a 65-microm DVB/PDMS phase showed better sensitivity towards these solvents when extracted from organic and aqueous matrix in comparison with the sensitivity obtained with direct injection approach. Extraction parameters such as extraction time, extraction stir rate, etc. are discussed. %RSD of peak area of replicate extraction was between 2 and 10% when 100 microm PDMS was used for extracting solvents from aqueous matrix. When DVB/PDMS fiber was evaluated for precision, %RSD of peak area from replicate extractions of solvents from organic matrix was between 2 and 8%. One-hundred micrometer PDMS showed excellent linearity from 10 to 500 microg/ml for analytes extracted from water solutions. On the other hand, DVB/PDMS phase showed better linearity than Carboxen/PDMS/DVB fiber when it was used to extract analytes in the concentration range of 10-5000 microg/ml from organic matrix.
authors.affiliation: Pharmacia Corporation, Global Chemical Process R&D, 4901 Searle Parkway, Skokie, IL 60077, USA. anil.r.raghani@pharmacia.com
authors.forename: A R
authors.initials: AR
authors.lastname: Raghani
mesh_terms: D000085:Acetates / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D005410:Flame Ionization; D008742:Methyl n-Butyl Ketone / Q000032:analysis; D012680:Sensitivity and Specificity; D012997:Solvents / Q000032:analysis*; D014835:Volatilization
chemical_list: D000085:Acetates; D012997:Solvents; D008742:Methyl n-Butyl Ketone; C007650:ethyl acetate; C005458:methyl isobutyl ketone