Characterization and quantification of Bcl-2 antisense G3139 and metabolites in plasma and urine by ion-pair reversed phase HPLC coupled with electrospray ion-trap mass spectrometry

Guowei Dai; Xiaohui Wei; Zhongfa Liu; Shujun Liu; Guido Marcucci; Kenneth K. Chan

doi:10.1016/j.jchromb.2005.05.049

Characterization and quantification of Bcl-2 antisense G3139 and metabolites in plasma and urine by ion-pair reversed phase HPLC coupled with electrospray ion-trap mass spectrometry

Guowei Dai, Xiaohui Wei, Zhongfa Liu, Shujun Liu, Guido Marcucci, Kenneth K. Chan

Research output: Contribution to journal › Article › peer-review

73 Scopus citations

Abstract

A novel ion-pair reversed phase electrospray ionization (IP-RP-ESI) liquid chromatography-mass spectrometry (LC-MS) method has been developed for identification and quantification of Bcl-2 antisense phosphorothioate oligonucleotides G3139 and metabolites in plasma. This method utilized solid phase extraction for desalting and matrix removal and detection by an ion trap mass spectrometer. Resolution was accomplished on a micro C18 column eluted with a mobile phase consisting of hexafluoro-2-propanol and triethylamine in methanol at 50 °C. Five G3139 metabolites were identified in plasma and urine from treated patients and rats. A cassette HPLC-MS/MS quantification method for G3139 and three metabolites was developed and validated with a limit of quantification (LOQ) of 17.6 nM in human and rat plasma with acceptable precision and accuracy. Plasma pharmacokinetics of G3139 and metabolites in these species were described.

Original language	English (US)
Pages (from-to)	201-213
Number of pages	13
Journal	Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume	825
Issue number	2
DOIs	https://doi.org/10.1016/j.jchromb.2005.05.049
State	Published - Oct 25 2005
Externally published	Yes

Bibliographical note

Funding Information:
We thank Drs. Jef Rozenski (Katholieke Universiteit Leuven, Belgium) and James A. McCloskey (University of Utah) for providing the SOS program used in this work. This research was supported in part by grants R21 CA94552 from the National Cancer Institute, the National Institute of Health and by BioMedical Mass Spectrometry Laboratory of College of Pharmacy.

Keywords

Bcl-2 antisense
Metabolism
N-in-one quantification
Pharmacokinetics
Tandem mass spectrometry

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10.1016/j.jchromb.2005.05.049

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Dai, G., Wei, X., Liu, Z., Liu, S., Marcucci, G., & Chan, K. K. (2005). Characterization and quantification of Bcl-2 antisense G3139 and metabolites in plasma and urine by ion-pair reversed phase HPLC coupled with electrospray ion-trap mass spectrometry. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 825(2), 201-213. https://doi.org/10.1016/j.jchromb.2005.05.049

Characterization and quantification of Bcl-2 antisense G3139 and metabolites in plasma and urine by ion-pair reversed phase HPLC coupled with electrospray ion-trap mass spectrometry. / Dai, Guowei; Wei, Xiaohui; Liu, Zhongfa et al.
In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, Vol. 825, No. 2, 25.10.2005, p. 201-213.

Research output: Contribution to journal › Article › peer-review

Dai, G, Wei, X, Liu, Z, Liu, S, Marcucci, G & Chan, KK 2005, 'Characterization and quantification of Bcl-2 antisense G3139 and metabolites in plasma and urine by ion-pair reversed phase HPLC coupled with electrospray ion-trap mass spectrometry', Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, vol. 825, no. 2, pp. 201-213. https://doi.org/10.1016/j.jchromb.2005.05.049

Dai G, Wei X, Liu Z, Liu S, Marcucci G, Chan KK. Characterization and quantification of Bcl-2 antisense G3139 and metabolites in plasma and urine by ion-pair reversed phase HPLC coupled with electrospray ion-trap mass spectrometry. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 2005 Oct 25;825(2):201-213. doi: 10.1016/j.jchromb.2005.05.049

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abstract = "A novel ion-pair reversed phase electrospray ionization (IP-RP-ESI) liquid chromatography-mass spectrometry (LC-MS) method has been developed for identification and quantification of Bcl-2 antisense phosphorothioate oligonucleotides G3139 and metabolites in plasma. This method utilized solid phase extraction for desalting and matrix removal and detection by an ion trap mass spectrometer. Resolution was accomplished on a micro C18 column eluted with a mobile phase consisting of hexafluoro-2-propanol and triethylamine in methanol at 50 °C. Five G3139 metabolites were identified in plasma and urine from treated patients and rats. A cassette HPLC-MS/MS quantification method for G3139 and three metabolites was developed and validated with a limit of quantification (LOQ) of 17.6 nM in human and rat plasma with acceptable precision and accuracy. Plasma pharmacokinetics of G3139 and metabolites in these species were described.",

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author = "Guowei Dai and Xiaohui Wei and Zhongfa Liu and Shujun Liu and Guido Marcucci and Chan, {Kenneth K.}",

note = "Funding Information: We thank Drs. Jef Rozenski (Katholieke Universiteit Leuven, Belgium) and James A. McCloskey (University of Utah) for providing the SOS program used in this work. This research was supported in part by grants R21 CA94552 from the National Cancer Institute, the National Institute of Health and by BioMedical Mass Spectrometry Laboratory of College of Pharmacy. ",

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AU - Marcucci, Guido

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N2 - A novel ion-pair reversed phase electrospray ionization (IP-RP-ESI) liquid chromatography-mass spectrometry (LC-MS) method has been developed for identification and quantification of Bcl-2 antisense phosphorothioate oligonucleotides G3139 and metabolites in plasma. This method utilized solid phase extraction for desalting and matrix removal and detection by an ion trap mass spectrometer. Resolution was accomplished on a micro C18 column eluted with a mobile phase consisting of hexafluoro-2-propanol and triethylamine in methanol at 50 °C. Five G3139 metabolites were identified in plasma and urine from treated patients and rats. A cassette HPLC-MS/MS quantification method for G3139 and three metabolites was developed and validated with a limit of quantification (LOQ) of 17.6 nM in human and rat plasma with acceptable precision and accuracy. Plasma pharmacokinetics of G3139 and metabolites in these species were described.

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Characterization and quantification of Bcl-2 antisense G3139 and metabolites in plasma and urine by ion-pair reversed phase HPLC coupled with electrospray ion-trap mass spectrometry

Abstract

Bibliographical note

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