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

doi:10.1007/BF02493373

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 journal › Article › peer-review

3 Citations (Scopus)

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 language	English
Pages (from-to)	s157-s163
Number of pages	7
Journal	Chromatographia
Volume	55
Issue number	supp 1
DOIs	https://doi.org/10.1007/BF02493373
Publication status	Published - 2002
Externally published	Yes

Keywords

Column liquid chromatography
Clucuronidation
colon cancer cells
Drug Resistance

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/BF02493373

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@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",

issn = "1612-1112",

publisher = "Springer",

number = "supp 1",

}

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

SN - 1612-1112

VL - 55

SP - s157-s163

JO - Chromatographia

JF - Chromatographia

IS - supp 1

ER -

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

Keywords

UN SDGs

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