title: A Method Utilizing Ultra-High Performance Liquid Chromatography with Ultraviolet and Mass Spectrometric Detection for the Analysis of Material Extracts Produced during a Controlled Extraction Study.
abstract: Pharmaceutical packaging/delivery systems and medical devices are characterized via a controlled extraction study as part of the development process for new pharmaceutical products. The purpose of this study is to determine compounds that may be extracted from the packaging using various solvents and exposure conditions. Results generated from a controlled extraction study serve to evaluate the suitability of the materials in the package configuration as well as provide an assessment of compounds that may potentially leach into the drug product. Analysis of extract samples generated during a controlled extraction study is performed utilizing multiple analytical methodologies to help establish a complete extractable profile regardless of the polarity, volatility, or other unique physical properties of each compound that may be present. The work presented in this article describes a method for the analysis of non-volatile as well as thermally labile, or otherwise not suited for analysis by gas chromatography, semi-volatile compounds from extraction samples. An ultra-high performance liquid chromatographic system with both atmospheric chemical ionization mass spectrometric and ultra violet detectors is used as the platform for the method. Adequate separation and retention is achieved for a mix of model compounds representing a wide range of common extractables within a 22 min analysis time. Ionization of this diverse range of compounds is also achieved with acceptable responses in the total ion chromatography data. Finally, analysis of extraction samples directly, even those comprised of non-compatible organic solvents, is demonstrated with no significant impact on the chromatography. Three case studies are presented to further illustrate method performance and its use for controlled extraction samples.
  Pharmaceutical packaging/delivery systems and medical devices are characterized via a controlled extraction study as part of the development process for new pharmaceutical products. The purpose of this study is to determine compounds that may be extracted from the packaging using various solvents and exposure conditions. Results of this work serve to evaluate the suitability of the material for use in the package as well as provide an assessment of compounds that may potentially contaminate the drug product. Analysis of extract samples generated during a controlled extraction study is performed utilizing multiple analytical methodologies to help establish a complete extractable profile regardless of the unique physical properties of each compound that may be present. The work presented in this article describes a method for the analysis of non-volatile as well as semi-volatile compounds from extraction samples. Separation and detection of a diverse range of extractables were demonstrated in a 22 min analysis time. Three case studies are presented to further illustrate method performance and its use for controlled extraction samples.
authors.affiliation: cGMP Laboratory, Pharmaceutical Product Development, Inc. (PPD), 8551 Research Way, Suite 90, Middleton, WI 53562, United States Steve.Zdravkovic@ppdi.com.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Zdravkovic
authors.affiliation: cGMP Laboratory, Pharmaceutical Product Development, Inc. (PPD), 8551 Research Way, Suite 90, Middleton, WI 53562, United States.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Bruss
authors.affiliation: cGMP Laboratory, Pharmaceutical Product Development, Inc. (PPD), 8551 Research Way, Suite 90, Middleton, WI 53562, United States.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Piccoli
authors.affiliation: cGMP Laboratory, Pharmaceutical Product Development, Inc. (PPD), 8551 Research Way, Suite 90, Middleton, WI 53562, United States.
authors.forename: Derek M
authors.initials: DM
authors.lastname: Wood
mesh_terms: D061605:Administration, Intravenous; D002851:Chromatography, High Pressure Liquid; D003257:Consumer Product Safety; D004340:Drug Contamination; D016503:Drug Delivery Systems; D004349:Drug Packaging; D006358:Hot Temperature; D006801:Humans; D036501:Metered Dose Inhalers; D061214:Patient Safety; D011126:Polypropylenes / Q000737:chemistry; D011143:Polyvinyl Chloride / Q000737:chemistry; D018570:Risk Assessment; D012997:Solvents / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013678:Technology, Pharmaceutical / Q000379:methods*; D013997:Time Factors; D014835:Volatilization; D057188:Workflow
chemical_list: D011126:Polypropylenes; D012997:Solvents; D011143:Polyvinyl Chloride
keywords: Controlled extraction study; Extractables; LC/MS; Leachables; UHPLC/UV/MS