Linked Life Data

12271442

Source:http://linkedlifedata.com/resource/pubmed/id/12271442

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2002-9-24
pubmed:abstractText
Kahalalide F (KF) is a novel cyclic depsipeptide anticancer drug, which has shown anticancer activity both in vitro and in vivo especially against human prostate cancer cell lines. To characterize the pharmacokinetics of KF during a phase I clinical trial in patients with androgen refractory prostate cancer, a method was developed and validated for the quantitative analysis of KF in human plasma using high-performance liquid chromatography (HPLC) coupled to positive electrospray ionization tandem mass spectrometry (ESI-MS/MS). Microbore reversed-phase liquid chromatography (LC) performed with mobile phases containing trifluoroacetic acid, an additive commonly used for separating peptides, resulted in substantial suppression of the signal for KF on ESI-MS/MS. An alternative approach employing a basic mobile phase provided an excellent response for KF when detected in the positive ion mode. Plasma samples were prepared for LC MS/MS by solid-phase extraction on C(18) cartridges. The LC separation was performed on a Zorbax Extend C(18) column (150 x 2.1 mm i.d., particle size 5 micro m) with acetonitrile -10 mM aqueous ammonia (85 : 15, v/v) as the mobile phase, at a flow-rate of 0.20 ml min(-1). A butyric acid analogue of KF was used as the internal standard. The lower limit of quantitation (LLQ) using a 500 micro l sample volume was 1 ng ml(-1) and the linear dynamic range extended to 1000 ng ml(-1). The inter-assay accuracy of the assay was -15.1% at the LLQ and between -2.68 and -9.05% for quality control solutions ranging in concentration from 2.24 to 715 ng ml(-1). The inter-assay precision was 9.91% or better at these concentrations. The analyte was stable in plasma under all relevant conditions evaluated and for a period of 16 h after reconstituting plasma extracts for LC analysis at ambient temperature.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1076-5174
pubmed:author
pubmed:copyrightInfo
Copyright 2002 John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
992-1000
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Quantitative analysis of the novel depsipeptide anticancer drug Kahalalide F in human plasma by high-performance liquid chromatography under basic conditions coupled to electrospray ionization tandem mass spectrometry.
pubmed:affiliation
Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands.
pubmed:publicationType
Journal Article, Clinical Trial, Clinical Trial, Phase I