Determination of the glucuronide metabolites of the topoisomerase I inhibitors, 7-ethyl-10-hydroxy-camptothecin (SN-38) and NU-ICRF 505 by high performance liquid chromatography

J. Cummings, B T. Ethell, Gary Boyd, B. Burchell, J F. Smyth, D I. Jodrell

Research output: Contribution to journalArticle

Abstract

HPLC methods are presented for the determination of the topoisomerase I inhibitors 7-ethyl 10-hydroxycamptothecin (SN-38) and NU/ICRF 505, their chemical/enzymatic hydrolysis products and glucuronide metabolites in both aqueous media and biological specimens. Chromatographic conditions were optimised for baseline resolution of the water-soluble metabolites from their non-water soluble parent compounds while eetaining compatibility with both atmospheric pressure electrospray ionisation and electron impact ionisation mass spectrometric detection. Solid phase extraction sample preparation utilising a C2-bonded silica sorbent enabled simultaneous recovery of parent compounds and metabolites. The methodology was applied to determine the stability of SN-38 in aqueous media and identify the glucuronide metabolites of both compounds in incubations with the drug-metabolising enzyme UDP-glucuronosyltransferase, the de-conjugating enzyme β-glucuronidase and human colon cancer cells.
Original languageEnglish
Pages (from-to)s157-s163
Number of pages7
JournalChromatographia
Volume55
Issue numbersupp 1
DOIs
Publication statusPublished - 2002
Externally publishedYes

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irinotecan
Topoisomerase I Inhibitors
Camptothecin
Glucuronides
High performance liquid chromatography
Metabolites
High Pressure Liquid Chromatography
Glucuronosyltransferase
Atmospheric Pressure
Glucuronidase
Solid Phase Extraction
Enzymes
Silicon Dioxide
Electrospray ionization
Colonic Neoplasms
Impact ionization
Enzymatic hydrolysis
Hydrolysis
Sorbents
Electrons

Keywords

  • Column liquid chromatography
  • Clucuronidation
  • colon cancer cells
  • Drug Resistance

Cite this

@article{285e095f032f404b8ae1ecd2da422983,
title = "Determination of the glucuronide metabolites of the topoisomerase I inhibitors, 7-ethyl-10-hydroxy-camptothecin (SN-38) and NU-ICRF 505 by high performance liquid chromatography",
abstract = "HPLC methods are presented for the determination of the topoisomerase I inhibitors 7-ethyl 10-hydroxycamptothecin (SN-38) and NU/ICRF 505, their chemical/enzymatic hydrolysis products and glucuronide metabolites in both aqueous media and biological specimens. Chromatographic conditions were optimised for baseline resolution of the water-soluble metabolites from their non-water soluble parent compounds while eetaining compatibility with both atmospheric pressure electrospray ionisation and electron impact ionisation mass spectrometric detection. Solid phase extraction sample preparation utilising a C2-bonded silica sorbent enabled simultaneous recovery of parent compounds and metabolites. The methodology was applied to determine the stability of SN-38 in aqueous media and identify the glucuronide metabolites of both compounds in incubations with the drug-metabolising enzyme UDP-glucuronosyltransferase, the de-conjugating enzyme β-glucuronidase and human colon cancer cells.",
keywords = "Column liquid chromatography, Clucuronidation, colon cancer cells, Drug Resistance",
author = "J. Cummings and Ethell, {B T.} and Gary Boyd and B. Burchell and Smyth, {J F.} and Jodrell, {D I.}",
year = "2002",
doi = "10.1007/BF02493373",
language = "English",
volume = "55",
pages = "s157--s163",
journal = "Chromatographia",
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}

Determination of the glucuronide metabolites of the topoisomerase I inhibitors, 7-ethyl-10-hydroxy-camptothecin (SN-38) and NU-ICRF 505 by high performance liquid chromatography. / Cummings, J.; Ethell, B T.; Boyd, Gary; Burchell, B.; Smyth, J F.; Jodrell, D I.

In: Chromatographia, Vol. 55 , No. supp 1, 2002, p. s157-s163.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Determination of the glucuronide metabolites of the topoisomerase I inhibitors, 7-ethyl-10-hydroxy-camptothecin (SN-38) and NU-ICRF 505 by high performance liquid chromatography

AU - Cummings, J.

AU - Ethell, B T.

AU - Boyd, Gary

AU - Burchell, B.

AU - Smyth, J F.

AU - Jodrell, D I.

PY - 2002

Y1 - 2002

N2 - HPLC methods are presented for the determination of the topoisomerase I inhibitors 7-ethyl 10-hydroxycamptothecin (SN-38) and NU/ICRF 505, their chemical/enzymatic hydrolysis products and glucuronide metabolites in both aqueous media and biological specimens. Chromatographic conditions were optimised for baseline resolution of the water-soluble metabolites from their non-water soluble parent compounds while eetaining compatibility with both atmospheric pressure electrospray ionisation and electron impact ionisation mass spectrometric detection. Solid phase extraction sample preparation utilising a C2-bonded silica sorbent enabled simultaneous recovery of parent compounds and metabolites. The methodology was applied to determine the stability of SN-38 in aqueous media and identify the glucuronide metabolites of both compounds in incubations with the drug-metabolising enzyme UDP-glucuronosyltransferase, the de-conjugating enzyme β-glucuronidase and human colon cancer cells.

AB - HPLC methods are presented for the determination of the topoisomerase I inhibitors 7-ethyl 10-hydroxycamptothecin (SN-38) and NU/ICRF 505, their chemical/enzymatic hydrolysis products and glucuronide metabolites in both aqueous media and biological specimens. Chromatographic conditions were optimised for baseline resolution of the water-soluble metabolites from their non-water soluble parent compounds while eetaining compatibility with both atmospheric pressure electrospray ionisation and electron impact ionisation mass spectrometric detection. Solid phase extraction sample preparation utilising a C2-bonded silica sorbent enabled simultaneous recovery of parent compounds and metabolites. The methodology was applied to determine the stability of SN-38 in aqueous media and identify the glucuronide metabolites of both compounds in incubations with the drug-metabolising enzyme UDP-glucuronosyltransferase, the de-conjugating enzyme β-glucuronidase and human colon cancer cells.

KW - Column liquid chromatography

KW - Clucuronidation

KW - colon cancer cells

KW - Drug Resistance

U2 - 10.1007/BF02493373

DO - 10.1007/BF02493373

M3 - Article

VL - 55

SP - s157-s163

JO - Chromatographia

JF - Chromatographia

SN - 0009-5893

IS - supp 1

ER -