title: Solid phase extraction in tandem with GC/MS for the determination of semi-volatile organic substances extracted from pharmaceutical packaging/delivery systems via aqueous solvent systems.
abstract: An extractable survey is one of several studies performed on a pharmaceutical storage/delivery system as part of the process of demonstrating that the system is suitable for its intended use. In this paper, a solid phase extraction method for the preparation of aqueous extracts generated during an extractable survey is presented. The method offers a convenient means to isolate semi-volatile organic extractable compounds from aqueous extraction solvents for analysis by gas chromatography/mass spectrometry. Following the solid phase extraction procedure, derivatization is performed to convert problematic functionalities (such as amines and acids) into appropriate chromatographically friendly derivatives. Demonstration of method performance is achieved in three ways using a set of 31 commonly observed extractable substances as model compounds. First, a breakthrough experiment was performed with a 2 solvent system consisting of water and 10/90 isopropanol/water over a range of 6 mL to 100 mL. Results from this experiment show only caprolactam possessed a significant level of breakthrough in either solvent over the range of volumes evaluated. Second, a formal accuracy/precision study was conducted using a three solvent system consisting of water, 10/90 isopropanol/water and 1% polysorbate 80. This experiment demonstrates the quantitative ability of the method at levels ranging from 20 ng/mL to 50 μg/mL. Recovery values of 70% to 130% of the theoretical concentration, with relative standard deviation values of less than 15% for replicate preparations, are obtained for a majority of the compounds evaluated. Finally, a case study involving the extraction of an intravenous drug delivery bag with multiple aqueous solvent systems further demonstrates the viability of solid phase extraction for use in an extractables survey.
authors.affiliation: Extractables/Leachables and GC/MS Services, Pharmaceutical Product Development, Inc., 8551 Research Way, Suite 90, Middleton, WI 53562, USA. Electronic address: steve.zdravkovic@ppdi.com.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Zdravkovic
mesh_terms: D002209:Caprolactam / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004349:Drug Packaging / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D052616:Solid Phase Extraction / Q000379:methods; D012997:Solvents / Q000737:chemistry*; D055549:Volatile Organic Compounds / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D012997:Solvents; D055549:Volatile Organic Compounds; D014867:Water; D002209:Caprolactam
keywords: Controlled extraction study; Extractables; GC/MS; Polysorbate 80; Solid phase extraction