University of North Florida
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Stuart Chalk, Ph.D.
Department of Chemistry
University of North Florida
Phone: 1-904-620-1938
Fax: 1-904-620-3535
Email: schalk@unf.edu
Website: @unf

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Pharmaceutical Research

  • Publisher: Springer
  • FAD Code: PHRS
  • CODEN: PHREEB
  • ISSN: 0724-8741
  • Abbreviation: Pharm. Res.
  • DOI Prefix: 10.1007/s11095-
  • Language: English
  • Comments: Fulltext from 1984 V1

Citations 4

"Sialic Acid 9-O-Acetylesterase Catalyzes The Hydrolyzing Reaction From Alacepril To Deacetylalacepril"
Pharm. Res. 2003 Volume 20, Issue 8 Pages 1309-1316
Shigeyuki Usui, Masafumi Kubota, Kazuhiro Iguchi, Tadashi Kiho, Tadashi Sugiyama, Yoshihiro Katagiri and Kazuyuki Hirano

Abstract: Purpose. In this work, the alacepril thiolesterase, which catalyzes the hydrolyzing reaction of the thiolester linkage in alacepril and the conversion from alacepril to deacetylalacepril, was purified from rat liver cytosol and characterized. Methods. A purification procedure for the thiolesterase consisted of ammonium sulfate fractionation and chromatographies with phenyl Sepharose CL-4B, Q Sepharose FF, ceramic hydroxylapatite, and phenyl Sepharose HP. The thiolesterase activity was assayed for alacepril as a substrate and the reaction product, deacetylalacepril, was measured using high-performance liquid chromatography. Results. The purified thiolesterase is heterodimeric with a molecular mass of 29 and 36 kDa subunits as estimated by sodium dodecyl sulfate -polyacrylamide gel electrophoresis. N-terminal amino acid sequence of these subunits reveals that the thiolesterase is identical to sialic acid 9-O-acetylesterase. The thiolesterase hydrolyzes not only the thiolester bond in alacepril, spironolactone, and acetyl coenzyme A but also the carboxylester bond in agr-naphtyl acetate. The alacepril thiolestrase activity is competitively inhibited by agr-naphtyl acetate. Conclusion. The thiolesterase, i.e., sialic acid 9-O-acetylesterase, seems to be involved in the metabolism of certain drugs such as alacepril and spironolactone. However, drugs having ester-type and amide-type linkages, for example dilazep, aniracetam, and benazepril, are not substrates for the thiolestrase.

"Mass Spectrometry Innovations In Drug Discovery And Development"
Pharm. Res. 2001 Volume 18, Issue 2 Pages 131-145
Damon I. Papac, Zahra Shahrokh

Abstract: This review highlights the many roles mass spectrometry plays in the discovery and development of new therapeutics by both the pharmaceutical and the biotechnology industries. Innovations in mass spectrometer source design, improvements to mass accuracy, and implementation of computer-controlled automation have accelerated the purification and characterization of compounds derived from combinatorial libraries, as well as the throughput of pharmacokinetics studies. The use of accelerator mass spectrometry, chemical reaction interface-mass spectrometry and continuous flow-isotope ratio mass spectrometry are promising alternatives for conducting mass balance studies in man. To meet the technical challenges of proteomics, discovery groups in biotechnology companies have led the way to development of instruments with greater sensitivity and mass accuracy (e.g., MALDI-TOF, ESI-Q-TOF, Ion Trap), the miniaturization of separation techniques and ion sources (e.g., capillary HPLC and nanospray), and the utilization of bioinformatics. Affinity-based methods coupled to mass spectrometry are allowing rapid and selective identification of both synthetic and biological molecules. With decreasing instrument cost and size and increasing reliability, mass spectrometers are penetrating both the manufacturing and the quality control arenas. The next generation of technologies to simplify the investigation of the complex fate of novel pharmaceutical entities in vitro and in vivo will be chip-based approaches coupled with mass spectrometry.

"Quantification Of Imipenem's Primary Metabolite In Plasma By Post-column Chemical Rearrangement And UV Detection"
Pharm. Res. 1991 Volume 8, Issue 1 Pages 33-39
Donald G. Musson, Richard Hajdu, William F. Bayne and John D. Rogers

Abstract: Pre-treated samples (prep. described) were subjected to HPLC on a column (10 cm x 8 mm) of Resolve C18 Radial-PAK equipped with a column of RCSS Guard PAK C18 with a mobile phase of tetrabutylammonium hydrogen sulfate - H3PO4 - water, adjusted to pH 6.85 with 1 M KOH. The eluate was diluted with 0.426 M H3PO4 (0.6 mL min-1, passed through a column (25 cm x 4.6 mm) packed with 40 µm glass beads and the absorbance was measured at 295 and 320 nm. Calibration graphs were rectilinear for 1 to 100 µg mL-1 of the cited metabolite (I) in plasma and dialysate and for 5 to 100 µg mL-1 in urine . Coefficients of variation were 10%.
Imipenem, N-Formimidoyl thienamycin Blood Plasma Urine HPLC Spectrophotometry Column Glass beads pH Post-column derivatization

"Analysis Of The Antimalarial Sesquiterpene Artemisinin In Artemisia Annua By High Performance Liquid Chromatography (HPLC) With Post-column Derivatization And Ultra-violet Detection"
Pharm. Res. 1987 Volume 4, Issue 3 Pages 258-260
Hala N. ElSohly, E. M. Croom and M. A. ElSohly

Abstract: Leaves of A. annua were dried at 40°C for 24 h, crushed and extracted by boiling under reflux with hexane. The extract was evaporated at 40°C in vacuo and a solution of the residue in acetonitrile was filtered before HPLC analysis, with acetophenone as internal standard, on a column (30 cm x 3.9 mm) of µBondapak C18 (10 µm) with a C18 guard column (1.5 cm x 3.2 mm), acetonitrile - acetate buffer solution of pH 5.1 (11:9) as mobile phase (0.45 mL min-1), post-column derivatization with methanolic KOH at 70°C in a knitted PTFE capillary and detection at 289 nm. The detection limit was 25 ng of artemisinin(I) and response was rectilinear up to 250 ng mL-1. Recovery of I from the plant was 89%.
Artemisinin Leaves HPLC Spectrophotometry Heated reaction Post-column derivatization Knotted reactor