Quantification of 1D, a novel derivative of curcumin with potential antitumor activity, in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study in rats

Context: 1 D is a novel derivative of curcumin and shows very promising antitumor activities in various cancer cell lines. Objective: To characterize its preclinical pharmacokinetic profiles, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the...

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Autores principales: Jialin Sun, Tao Jiang, Wen Xu, Zhangying Feng, Xianghua Quan, Ping Leng, Wei Sun, Jun Zhao, Fanbo Jing, Jing Li
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Publicado: Taylor & Francis Group 2019
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spelling oai:doaj.org-article:4bda032e6812435da947930f4b12d91c2021-11-17T14:21:56ZQuantification of 1D, a novel derivative of curcumin with potential antitumor activity, in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study in rats1388-02091744-511610.1080/13880209.2019.1603243https://doaj.org/article/4bda032e6812435da947930f4b12d91c2019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1603243https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: 1 D is a novel derivative of curcumin and shows very promising antitumor activities in various cancer cell lines. Objective: To characterize its preclinical pharmacokinetic profiles, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of 1 D in rat plasma. Materials and methods: An aliquot of 50 μL plasma sample was processed by protein precipitation with methanol. Chromatographic separation was accomplished on a Zorbax Eclipse Plus C18 column (2.1 mm × 50 mm, 1.8 μm) with a gradient elution system (water/0.1% formic acid and methanol). Detection was performed by multiple reaction monitoring (MRM) mode using electrospray ionization in the positive ion mode. The optimized fragmentation transition for 1 D was m/z 491.2 → 361.2. Results: The method was linear over the concentration range of 5–1000 ng/mL. The intra- and inter-day precisions were less than 9.8% and the accuracy was within ± 14.5%. The mean recovery of 1 D ranged from 102.5 to 105.9%. No matrix effects and significant sample loss during sample processing were observed. The validated method has been successfully applied to a pharmacokinetic study in rats after intravenous administration of 1 D. Non-compartmental pharmacokinetic parameters, including half-life (t1/2), apparent volume of distribution (Vz), clearance (CLz), and area under the concentration-time curve (AUC(0–t)) were 4.92 h, 46.56 L/kg, 6.33 L/h/kg, and 806.70 μg/L/h, respectively. Discussion and conclusions: Results demonstrated that 1 D displayed favourable pharmacokinetic properties for further in vivo pharmacologic evaluation, which could be facilitated by the validated LC-MS/MS method.Jialin SunTao JiangWen XuZhangying FengXianghua QuanPing LengWei SunJun ZhaoFanbo JingJing LiTaylor & Francis Grouparticleisothiouronium-modified pyrimidine-substituted curcuminlc-ms/msintravenousTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 287-294 (2019)
institution DOAJ
collection DOAJ
language EN
topic isothiouronium-modified pyrimidine-substituted curcumin
lc-ms/ms
intravenous
Therapeutics. Pharmacology
RM1-950
spellingShingle isothiouronium-modified pyrimidine-substituted curcumin
lc-ms/ms
intravenous
Therapeutics. Pharmacology
RM1-950
Jialin Sun
Tao Jiang
Wen Xu
Zhangying Feng
Xianghua Quan
Ping Leng
Wei Sun
Jun Zhao
Fanbo Jing
Jing Li
Quantification of 1D, a novel derivative of curcumin with potential antitumor activity, in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study in rats
description Context: 1 D is a novel derivative of curcumin and shows very promising antitumor activities in various cancer cell lines. Objective: To characterize its preclinical pharmacokinetic profiles, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of 1 D in rat plasma. Materials and methods: An aliquot of 50 μL plasma sample was processed by protein precipitation with methanol. Chromatographic separation was accomplished on a Zorbax Eclipse Plus C18 column (2.1 mm × 50 mm, 1.8 μm) with a gradient elution system (water/0.1% formic acid and methanol). Detection was performed by multiple reaction monitoring (MRM) mode using electrospray ionization in the positive ion mode. The optimized fragmentation transition for 1 D was m/z 491.2 → 361.2. Results: The method was linear over the concentration range of 5–1000 ng/mL. The intra- and inter-day precisions were less than 9.8% and the accuracy was within ± 14.5%. The mean recovery of 1 D ranged from 102.5 to 105.9%. No matrix effects and significant sample loss during sample processing were observed. The validated method has been successfully applied to a pharmacokinetic study in rats after intravenous administration of 1 D. Non-compartmental pharmacokinetic parameters, including half-life (t1/2), apparent volume of distribution (Vz), clearance (CLz), and area under the concentration-time curve (AUC(0–t)) were 4.92 h, 46.56 L/kg, 6.33 L/h/kg, and 806.70 μg/L/h, respectively. Discussion and conclusions: Results demonstrated that 1 D displayed favourable pharmacokinetic properties for further in vivo pharmacologic evaluation, which could be facilitated by the validated LC-MS/MS method.
format article
author Jialin Sun
Tao Jiang
Wen Xu
Zhangying Feng
Xianghua Quan
Ping Leng
Wei Sun
Jun Zhao
Fanbo Jing
Jing Li
author_facet Jialin Sun
Tao Jiang
Wen Xu
Zhangying Feng
Xianghua Quan
Ping Leng
Wei Sun
Jun Zhao
Fanbo Jing
Jing Li
author_sort Jialin Sun
title Quantification of 1D, a novel derivative of curcumin with potential antitumor activity, in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study in rats
title_short Quantification of 1D, a novel derivative of curcumin with potential antitumor activity, in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study in rats
title_full Quantification of 1D, a novel derivative of curcumin with potential antitumor activity, in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study in rats
title_fullStr Quantification of 1D, a novel derivative of curcumin with potential antitumor activity, in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study in rats
title_full_unstemmed Quantification of 1D, a novel derivative of curcumin with potential antitumor activity, in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study in rats
title_sort quantification of 1d, a novel derivative of curcumin with potential antitumor activity, in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study in rats
publisher Taylor & Francis Group
publishDate 2019
url https://doaj.org/article/4bda032e6812435da947930f4b12d91c
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