Degradation kinetics of larotaxel and identification of its degradation products in alkaline condition

Larotaxel, a new taxane compound prepared by partial synthesis from 10-deacetyl baccatin III, is active against tumors. In this research, a selective LC–MS method was developed and validated for the study of degradation kinetics of larotaxel, which was carried out in aqueous solutions with different...

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Published inJournal of pharmaceutical analysis Vol. 7; no. 2; pp. 118 - 122
Main Authors Liang, Xiaoming, Liu, Zhenzhen, Shi, Huiyan, Zhang, Yuanyuan, Wang, Shixiao, Bi, Kaishun, Chen, Xiaohui
Format Journal Article
LanguageEnglish
Published China Elsevier B.V 01.04.2017
Xi'an Jiaotong University, Journal of Pharmaceutical Analysis
Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China%Department of Functional Science, School of Medicine, Yangtze University, No.1 Nanhuan Road, Jingzhou City 434100, China
Xi'an Jiaotong University
Elsevier
Subjects
Aqueous solutions
Calibration
Cell division
Chromatography
Degradation kinetics
Degradation products
High-performance liquid chromatography
Identification
Ions
Kinetics
Larotaxel
Lung cancer
Mass spectrometry
Original
pH effects
Scientific imaging
Sensors
Temperature
Temperature effects
Tumors
United States > US
China
Japan
pH
Temperature
Larotaxel
Degradation products
Degradation kinetics
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Summary:Larotaxel, a new taxane compound prepared by partial synthesis from 10-deacetyl baccatin III, is active against tumors. In this research, a selective LC–MS method was developed and validated for the study of degradation kinetics of larotaxel, which was carried out in aqueous solutions with different pH（1.5, 3.0, 5.0, 6.5, 7.4, 9.0, 10 and 11.0） and temperature（0, 25, 37 and 45 °C）. The linear range was 0.5–25 μg/mL, the intra-and inter-day precisions were less than 7.0%, and accuracy ranged from 97.4–104.5% for each analyte. The observed rate obtained by measuring the remaining intact larotaxel was shown to follow first-order kinetics. The activation energies for degradation were 126.7 and 87.01 k J/mol at pH 1.5 and 11, respectively. Although larotaxel was stable in pH 5, 6.5 and 7.4 buffers at 37 °C for 24 h during our study, increasing or decreasing the pH of the solutions would decrease its stabilities. Moreover, three main degradation products in alkaline condition were separated by HPLC and identified by Q–TOF–MS. The three degradation products were confirmed as 10-deacetyl larotaxel, 7, 8-cyclopropyl baccatin Ⅲ and 10-deacetyl-7, 8-cyclopropyl baccatin Ⅲ.
Bibliography:61-1484/R
Larotaxel, a new taxane compound prepared by partial synthesis from 10-deacetyl baccatin III, is active against tumors. In this research, a selective LC–MS method was developed and validated for the study of degradation kinetics of larotaxel, which was carried out in aqueous solutions with different pH（1.5, 3.0, 5.0, 6.5, 7.4, 9.0, 10 and 11.0） and temperature（0, 25, 37 and 45 °C）. The linear range was 0.5–25 μg/mL, the intra-and inter-day precisions were less than 7.0%, and accuracy ranged from 97.4–104.5% for each analyte. The observed rate obtained by measuring the remaining intact larotaxel was shown to follow first-order kinetics. The activation energies for degradation were 126.7 and 87.01 k J/mol at pH 1.5 and 11, respectively. Although larotaxel was stable in pH 5, 6.5 and 7.4 buffers at 37 °C for 24 h during our study, increasing or decreasing the pH of the solutions would decrease its stabilities. Moreover, three main degradation products in alkaline condition were separated by HPLC and identified by Q–TOF–MS. The three degradation products were confirmed as 10-deacetyl larotaxel, 7, 8-cyclopropyl baccatin Ⅲ and 10-deacetyl-7, 8-cyclopropyl baccatin Ⅲ.
Larotaxel Degradation kinetics pH Temperature Degradation products
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2095-1779
2214-0883
DOI:10.1016/j.jpha.2016.11.002