Clinical Chemistry
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Clinical Chemistry 43: 505-510, 1997;
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(Clinical Chemistry. 1997;43:505-510.)
© 1997 American Association for Clinical Chemistry, Inc.

Articles

HPLC method for monitoring SDZ PSC 833 in whole blood

Mitchell G. Scott1,a, Karl G. Hock1, Daniel L. Crimmins2 and Paula M. Fracasso3

1 Division of Laboratory Medicine (Box 8118),
2 Department of Molecular Biology and Pharmacology, Protein and Nucleic Acid Chemistry Laboratory (Box 8103), and
3 Department of Medicine (Box 8056), Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110.
a Author for correspondence and reprint requests. Fax 314-362-1461; e-mail mscott{at}labmed.wustl.edu

P-glycoprotein (Pgp) is a 170-kDa membrane transporter that mediates drug efflux and is an effector of multidrug resistance. SDZ PSC 833 (PSC), a nonimmunosuppressive cyclosporine that potently modulates Pgp, is currently under clinical evaluation in patients with cancer. We have developed a reversed-phase HPLC assay for determining PSC blood concentrations that utilizes a step gradient with linear segments to resolve PSC into two distinct peaks (likely to be keto and enol isomers). To clinically validate the assay, PSC concentrations were obtained by HPLC from nine patients receiving oral doses of 5 mg/kg every 6 h. Values ranged from 0.91 to 5.4 mg/L during the dosing period, comparable with concentrations of PSC that modulate Pgp in vitro. In addition, we investigated the immunoreactivity of the Abbott TDx cyclosporin A (CsA) monoclonal whole-blood assay for PSC. The TDx CsA assay cross-reacts ~17% with PSC as determined by adding known amounts of PSC to whole blood. When PSC concentrations obtained by the TDx CsA assay were divided by 0.17, we found agreement between the TDx CsA assay and the HPLC PSC assay for samples from nine patients.


Key Words: indexing terms: P-glycoprotein • multidrug resistance • cyclosporine




The following articles in journals at HighWire Press have cited this article:


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 Clin. Chem.Home page
D. Chen, D. L. Crimmins, F. F. Hsu, F. P. Lindberg, and M. G. Scott
Hemoglobin Raleigh as the cause of a falsely increased hemoglobin A1C in an automated ion-exchange HPLC method
Clin. Chem., June 1, 1998; 44(6): 1296 - 1301.
[Abstract] [Full Text] [PDF]


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Copyright © 1997 by the American Association for Clinical Chemistry.