Document Detail


Quantitative determination of peptide drug in human plasma samples at low pg/ml levels using coupled column liquid chromatography-tandem mass spectrometry.
MedLine Citation:
PMID:  20456896     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Plasma concentrations after administration of peptide drugs are often low due to the high potency often seen with this class of compounds. In this work a bioanalytical method based on coupled column liquid chromatography-tandem mass spectrometry (LC-MS/MS) is presented for quantification of a peptide drug, FE 202158, under clinical development. A volume of 0.5 ml human plasma is solid phase extracted on a weak cationic exchanger. After evaporation of the solvent to dryness, the reconstituted sample is injected into a coupled column liquid chromatography system. A heart-cut from the initial column, a cyano column, is trapped on a C(4) column and thereafter injected into a microbore C(18) column. For the detection a triple quadrupole mass spectrometer, equipped with a TurboIonSpray interface working in positive ion mode, is used. The design of the system is described and the gain in sensitivity and selectivity, compared to a conventional system, is discussed. Data from validation of the bioanalytical method are presented. For human plasma samples a lower limit of quantification (LLOQ) of 5.00 pg/ml (=4.77 pmol/l) was achieved. The inter-assay precision was less than 11% and bias was within +/-4% over the whole validated range of 5.00-860 pg/ml.
Authors:
Ulf Lövgren; Sara Johansson; Lasse Skov Jensen; Carina Ekström; Alf Carlshaf
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Publication Detail:
Type:  Journal Article     Date:  2010-03-27
Journal Detail:
Title:  Journal of pharmaceutical and biomedical analysis     Volume:  53     ISSN:  1873-264X     ISO Abbreviation:  J Pharm Biomed Anal     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-07-20     Completed Date:  2010-09-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309336     Medline TA:  J Pharm Biomed Anal     Country:  England    
Other Details:
Languages:  eng     Pagination:  537-45     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier B.V. All rights reserved.
Affiliation:
Department of Bioanalysis, Experimental Medicine & Bioanalysis, Clinical & Non-Clinical R & D, Ferring Pharmaceuticals A/S, Kay Fiskers Plads 11, 2300 Copenhagen S, Denmark. ulf.lovgren@ferring.com
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MeSH Terms
Descriptor/Qualifier:
Chromatography, Liquid / methods*
Humans
Peptides / blood*
Pharmaceutical Preparations / blood*
Sensitivity and Specificity
Solid Phase Extraction
Tandem Mass Spectrometry / methods*
Chemical
Reg. No./Substance:
0/Peptides; 0/Pharmaceutical Preparations

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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