Determination of digoxin in human plasma by LC-MS/MS and its application in pediatric patients

XIA Ying; LONG Jiayi; DAI Haoran; SHEN Mengyuan; GUO Hongli; HU Yahui; CHEN Feng

doi:10.11665/j.issn.1000-5048.20210610

Journal of China Pharmaceutical University > 2021 > 52(6): 719-724. > DOI: 10.11665/j.issn.1000-5048.20210610

XIA Ying, LONG Jiayi, DAI Haoran, SHEN Mengyuan, GUO Hongli, HU Yahui, CHEN Feng. Determination of digoxin in human plasma by LC-MS/MS and its application in pediatric patients[J]. Journal of China Pharmaceutical University, 2021, 52(6): 719-724. DOI: 10.11665/j.issn.1000-5048.20210610

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Determination of digoxin in human plasma by LC-MS/MS and its application in pediatric patients

1.
Pharmaceutical Sciences Research Center, Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing 210008
2.
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009
3.
Kangda College of Nanjing Medical University, Lianyungang 222000 , China

Funds: This study was supported by Specially-Appointed Medical Expert Project of Jiangsu Provincial Commission of Health (2019)

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Received Date: August 23, 2021
Revised Date: November 03, 2021

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Abstract

Abstract

The aim of the study was to develop a simple, rapid and accurate LC-MS/MS method for the determination of digoxin.Digoxin-d3 was taken as the internal standard (IS), and sample preparation was achieved by liquid-liquid extraction.Chromatographic separation was performed on a Kinetex C₁₈ column (2.1 mm × 50 mm, 2.6 μm; Phenomenex) using an isocratic elution with merely 2 min for each sample.The mobile phase consisted of water and acetonitrile solutions, both containing 1 mmol/L ammonium acetate and 1 mmol/L formic acid (55∶45).The detection was conducted on a TripleQuad^TM 4500MD mass spectrometer coupled with electrospray ionization interface under positive-ion multiple reaction monitoring mode.The transitions were m/z 798.5 → 651.3 and m/z 801.6 → 654.4 for digoxin and digoxin-d3, respectively.Results showed that the method was linear over the range of 0.100-20.0 ng/mL.The selectivity, accuracy and precision, recovery and stability of the method were all within the acceptable limits with no matrix effect.This method was successfully applied to a girl treated with digoxin with substantial improvement of therapeutic effect and elimination of toxic reaction, so it can provide valuable fuidance and reference for individualized medication in clinical practice.
- digoxin,
- LC-MS/MS,
- children,
- determination of contents

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References

[1]	. Crit Pathw Cardiol，2011，10（2）：93-98.
[2]	Abdel Jalil MH，Abdullah N，Alsous MM，et al. A systematic review of population pharmacokinetic analyses of digoxin in the paediatric population［J］. Br J Clin Pharmacol，2020，86（7）：1267-1280.
[3]	Grzesk G，Stolarek W，Kasprzak M，et al. Therapeutic drug monitoring of digoxin-20 years of experience［J］. Pharmacol Rep，2018，70（1）：184-189.
[4]	Li S，Liu G，Jia J，et al. Therapeutic monitoring of serum digoxin for patients with heart failure using a rapid LC-MS/MS method［J］. Clin Biochem，2010，43（3）：307-313.
[5]	Li WJ，Xu J，Xu J，et al. Data analysis of monitoring for 4 therapeutic drugs in children''s hospital ［J］. Chin New Drug J（中国新药杂志），2014，（13）：1587-1592.
[6]	Xia Y，Guo HL，Hu YH，et al. Therapeutic drug monitoring for monoclonal antibody：progress in the appli-cation of LC-MS/MS technique ［J］. J China Pharm Univ（中国药科大学学报），2021，52（1）：122-128.
[7]	Shi S，Li Z，Chen H，et al. Development and validation of an LC-MS method with electrospray ionization for quantitation of digoxin in human plasma and urine：application to a pharmacokinetic study［J］. J Chromatogr B Analyt Technol Biomed Life Sci，2008，875（2）：405-410.
[8]	Kirby BJ，Kalhorn T，Hebert M，et al. Sensitive and specific LC-MS assay for quantification of digoxin in human plasma and urine［J］. Biomed Chromatogr，2008，22（7）：712-718.
[9]	Bylda C，Thiele R，Kobold U，et al. Simultaneous quantification of digoxin，digitoxin，and their metabolites in serum using high performance liquid chromatography-tandem mass spectrometry［J］. Drug Test Anal，2015，7（10）：937-946.
[10]	Li X，Wang Y，Zhou Q，et al. A sensitive method for digoxin determination using formate-adduct ion based on the effect of ionization enhancement in liquid chromatograph-mass spectrometer［J］. J Chromatogr B Analyt Technol Biomed Life Sci，2015，978-979：138-144. doi：10.1016/j.jchromb.2014. 11.023.
[11]	Hirabayashi H，Sugimoto H，Matsumoto S，et al. Development of a quantification method for digoxin，a typical P-glycoprotein probe in clinical and non-clinical studies，using high performance liquid chromatography-tandem mass spectrometry：the usefulness of negative ionization mode to avoid competitive adduct-ion formation［J］. J Chromatogr B Analyt Technol Biomed Life Sci，2011，879（32）：3837-3844.
[12]	Mitamura K，Horikawa A，Yamane Y，et al. Determination of digoxin in human serum using stable isotope dilution liquid chromatography/electrospray ionization-tandem mass spectrometry［J］. Biol Pharm Bull，2007，30（9）：1653-1656.
[13]	Hashimoto Y，Shibakawa K，Nakade S，et al. Validation and application of a 96-well format solid-phase extraction and liquid chromatography-tandem mass spectrometry method for the quantitation of digoxin in human plasma［J］. J Chromatogr B Analyt Technol Biomed Life Sci，2008，869（1/2）：126-132.
[14]	Xue X，Huang M，Xiao H，et al. Rapid and simultaneous measurement of midazolam，1''-hydroxymidazolam and digoxin by liquid chromatography/tandem mass spectrometry：application to an in vivo study to simultaneously measure P-glycoprotein and cytochrome P450 3A activity［J］. J Pharm Biomed Anal，2011，55（1）：187-193.

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