Determination of GTI-2040, a novel antisense oligonucleotide, in human plasma by using HPLC combined with solid phase and liquid–liquid extractions
GTI-2040 is a 20-mer phosphorothioate oligonucleotide complementary to the mRNA of the R2 subunit of ribonucleotide reductase (RNR). It is under clinical development as an anti-cancer agent. A reverse phase high-performance liquid chromatograph (HPLC) method was established for the quantitative anal...
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Published in | Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 829; no. 1; pp. 45 - 49 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Amsterdam
Elsevier B.V
27.12.2005
Elsevier Science |
Subjects | |
Online Access | Get full text |
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Summary: | GTI-2040 is a 20-mer phosphorothioate oligonucleotide complementary to the mRNA of the R2 subunit of ribonucleotide reductase (RNR). It is under clinical development as an anti-cancer agent. A reverse phase high-performance liquid chromatograph (HPLC) method was established for the quantitative analysis of GTI-2040 in human plasma. Plasma samples were prepared with an initial solid-phase extraction (SPE) followed by a liquid–liquid extraction step. HPLC analysis was performed with a gradient system on a Waters XTerra
®MS C18 column. The mobile phase consisted of acetonitrile–tetrabutyl ammonium hydrogen sulfate (TBAS) buffer (pH 9.0, 20
mM) at a flow rate of 1.0
ml/min, and the detector was set at a wavelength of 260
nm. A cationic pairing reagent, tetrabutyl ammonium hydrogen sulfate was added during plasma sample clean-up with solid-phase extraction, resulting in significant improvement in extraction recovery. In addition, TBAS addition to the mobile phase improved the peak symmetry of GTI-2040. This method was successfully used in the analysis of GTI-2040 in clinical plasma samples. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1570-0232 1873-376X |
DOI: | 10.1016/j.jchromb.2005.09.036 |