Direct determination of stability of protease inhibitors in plasma by HPLC with automated column-switching.

Abstract:

:Automated column-switching HPLC methods were developed and utilized for the direct analyses of three hydroxamic acid based metalloprotease inhibitors in rat plasma. These column-switching methods involved the use of a restricted-access media (RAM) precolumn and a column-switching valve, allowing the complete automation of sample preparation and HPLC. The plasma samples were directly injected onto a precolumn packed with SPS/ODS stationary phase and then backflushed onto an ODS analytical column using a 6-port column-switching device. The drug stability in rat plasma was determined using both the automated and traditional HPLC methods. The results obtained from the automated column-switching methods were in good agreement with those from traditional methods that involve sequential protein precipitation, liquid extraction, solvent evaporation, and sample reconstitution. In addition to the elimination of labor-intensive and time-consuming sample preparation procedures, the column-switching methods allowed on-line analyte enrichment and accurate determination of drug stability in plasma with detection limits in the range of 10-20 ng/ml(-1). This work represents, for the first time, a drug stability study in plasma by automated column-switching HPLC technique with the use of a RAM column. Our column-switching methods can be readily adapted to any existing HPLC system with minimal hardware modification.

journal_name

J Pharm Biomed Anal

authors

Peng SX,Strojnowski MJ,Bornes DM

doi

10.1016/s0731-7085(98)00127-7

subject

Has Abstract

pub_date

1999-03-01 00:00:00

pages

343-9

issue

3-4

eissn

0731-7085

issn

1873-264X

pii

S0731-7085(98)00127-7

journal_volume

19

pub_type

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