Joseph Tweed

Pfizer, New York, New York, United States

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Publications (3)8.47 Total impact

  • Eugene P Kadar · Yi Su · Yizhong Zhang · Joseph Tweed · Chad E Wujcik
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    ABSTRACT: The distribution coefficient, D, is a physicochemical property used to determine the partitioning of compounds between aqueous and hydrophobic media at a given pH. A clear relationship was observed between the calculated pH-dependent distribution coefficient of six representative pharmaceutical probe compounds and their propensity to partition between a relatively hydrophobic polypropylene surface and the aqueous matrices, human urine or human cerebrospinal fluid (CSF). Compound log D cut-off values of 1.5 and 3.8 for urine and CSF, respectively, were determined using a threshold of less than 20% adsorption to the polypropylene surface. The ability to forecast the adsorption of a given compound to a polypropylene container with urine and CSF offers an effective means for screening potential issues and identifying when additional testing and corrective measures may need to be applied.
    No preview · Article · Apr 2010 · Bioanalysis
  • Chad E Wujcik · Joseph Tweed · Eugene P Kadar
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    ABSTRACT: Hydrophilic retention coefficients for 17 peptides were calculated based on retention coefficients previously published for TSKgel silica-60 and were compared with the experimental elution profile on a Waters Atlantis HILIC silica column using TFA and methanesulfonic acid (MSA) as ion-pairing reagents. Relative peptide retention could be accurately determined with both counter-ions. Peptide retention and chromatographic behavior were influenced by the percent acid modifier used with increases in both retention and peak symmetry observed at increasing modifier concentrations. The enhancement of net peptide polarity through MSA pairing shifted retention out by nearly five-fold for the earliest eluting peptide, compared with TFA. Despite improvements in retention and efficiency (N(eff)) for MSA over TFA, a consistent reduction in calculated selectivity (alpha) was observed. This result is believed to be attributed to the stronger polar contribution of MSA masking and diminishing the underlying influence of the amino acid residues of each associated peptide. Finally, post-column infusion of propionic acid and acetic acid was evaluated for their potential to recover signal intensity for TFA and MSA counter-ions for LC-ESI-MS applications. Acetic acid generally yielded more substantial signal improvements over propionic acid on the TFA system while minimal benefits and some further reductions were noted with MSA.
    No preview · Article · Mar 2010 · Journal of Separation Science
  • Ang Liu · Joseph Tweed · Chad E Wujcik
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    ABSTRACT: Reversed phase and hydrophilic interaction chromatography (HILIC) were successfully coupled for the on-line extraction and quantitative analysis of peptides by ESI-LC-MS/MS. A total of 11 peptides were utilized to determine the conditions for proper focusing and separation on both dimensions. Minor modifications to the initial organic composition of the first reversed-phase dimension provided options between a comprehensive (generic) or more selective approach for peptide transfer to the second HILIC dimension. Ion-pairing with trifluoroacetic acid (TFA) provided adequate chromatographic retention and peak symmetry for the selected peptides on both C18 and HILIC. The resulting signal suppression from TFA was partially recovered by a post-column "TFA fix" using acetic acid yielding improvements in sensitivity. Minimal sample preparation aligned with standard on-line extraction procedures provided highly reproducible and robust results for over 300 sequential matrix injections. Final optimized conditions were successfully employed for the quantitation of peptide PTHrP (1-36) in rat K(3)EDTA plasma from 25.0 to 10,000 ng/mL using PTHrP (1-34) as the analog internal standard. This highly orthogonal two-dimensional configuration was found to provide the unique selectivity required to overcome issues with interfering endogenous components and minimize electrospray ionization effects in biological samples.
    No preview · Article · Aug 2009 · Journal of chromatography. B, Analytical technologies in the biomedical and life sciences