Document Detail

Assay for the quinocarmycin analog DX-52-1 in human plasma using high-performance liquid chromatography with automated column switching and low wavelength ultraviolet detection.
MedLine Citation:
PMID:  9766875     Owner:  NLM     Status:  MEDLINE    
The hydrocyanated derivative of the antitumor antibiotic quinocarmycin, DX-52-1 (I), exhibits impressive activity against human melanoma xenograft models in vivo. Phase I clinical trials to evaluate this compound as an antineoplastic agent have been initiated by the US National Cancer Institute. We have developed an HPLC assay for the determination of I in human plasma involving automated column switching and UV detection at 210 nm. The preparation of samples for chromatographic analysis entails the preliminary removal of plasma proteins by precipitation with acetonitrile, acidifying the clear supernatant to pH 4.5, then extracting twice with tert.-butyl methyl ether to recover the drug. A heart-cutting procedure employing two HPLC columns with contrasting retention characteristics under isocratic reversed-phase conditions was used to achieve the selectivity required for low wavelength UV detection of the analyte. The sample extract was initially loaded onto a column packed with a cyanopropyl stationary phase. During the predetermined time interval that I eluted from this column, a fully automated six-position switching valve was used to direct the effluent onto an octadecylsilane analytical column. The assay has been thoroughly validated with regard to linearity, inter- and intra-day accuracy and precision, recovery, selectivity and specificity. Using a sample volume of 1.0 ml, the lowest concentration of I quantified with acceptable day-to-day reproducibility was found to be 2.56 ng/ml (R.S.D. 18.9%, n=21, 4 months). This proved to be sufficiently sensitive for pharmacokinetic drug level monitoring in cancer patients treated with a 6-h continuous intravenous infusion of I, even at the starting dose of 3 mg/m2. The successful performance and reliability of the assay has been demonstrated through extensive application to the routine analysis of plasma specimens acquired during a phase I clinical trial of the drug.
J G Supko; J R Soglia; R V Nair
Related Documents :
4020635 - Fluorometric determination of phenylephrine hydrochloride by liquid chromatography in h...
22455645 - The development and validation of an assay for the quantification of the p. chrysogenum...
8491815 - Semi-automated solid-phase extraction procedure for drug screening in biological fluids...
11393715 - Rapid determination of citalopram in human plasma by high-performance liquid chromatogr...
12207295 - Large-volume sample stacking for analysis of ethylenediaminetetraacetic acid by capilla...
18078575 - A unified approach for the measurement of individual or total volatile organic sulfur c...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of chromatography. B, Biomedical sciences and applications     Volume:  714     ISSN:  1387-2273     ISO Abbreviation:  J. Chromatogr. B Biomed. Sci. Appl.     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1998-12-21     Completed Date:  1998-12-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9714109     Medline TA:  J Chromatogr B Biomed Sci Appl     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  341-53     Citation Subset:  IM    
Division of Hematology-Oncology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Antibiotics, Antineoplastic / blood*
Chromatography, High Pressure Liquid / methods*
Isoquinolines / blood
Reproducibility of Results
Sensitivity and Specificity
Spectrophotometry, Ultraviolet
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Isoquinolines; 96251-59-1/DX 52-1

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

Previous Document:  Determination of 2-n-propylquinoline in mouse plasma and liver by high-performance liquid chromatogr...
Next Document:  Trace analysis of SN-38 in human plasma by high-performance liquid chromatography.