LC–MS/MS method for simultaneous determination of diethylcarbamazine, albendazole and albendazole metabolites in human plasma: Application to a clinical pharmacokinetic study

Yashpal S. Chhonker, Constant Edi, Daryl J Murry

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Combination therapy with anti-filarial drugs is now widely used for treatment of lymphatic filariasis. A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) method was developed and validated for simultaneous quantitation of diethylcarbamazine (DEC), albendazole (ABZ) and albendazole metabolites in human plasma. Separation and detection of analytes were achieved on a reversed phase column (Acquity UPLC®BEH C18 column (100 × 2.1 mm, 1.7 μm) with gradient elution using 0.05% formic acid in methanol and 0.05% formic acid as mobile phase. Solid phase extraction was utilized for elution of analytes from the matrix. Thereafter, analytes were monitored by using MS/MS with electrospray ionization source in positive multiple reaction monitoring mode. The MS/MS response was linear over the concentration range from 0.1–200 ng/mL for ABZ and ABZ-ON, 0.5–1000 ng/mL for ABZ-OX and 1–2000 ng/mL for DEC with a correlation coefficient (r2) of 0.998 or better. The within- and between-batch precisions (relative standard deviation, % RSD) and the accuracy (% bias) were within the acceptable limits as per FDA guideline. The validated method was successfully applied to the clinical pharmacokinetic study. Due to high sensitivity and low requirement of sample volume, the method will be applicable for therapeutic drug monitoring of this regimen.

Original languageEnglish (US)
Pages (from-to)84-90
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume151
DOIs
StatePublished - Mar 20 2018

Fingerprint

Diethylcarbamazine
Plasma applications
Albendazole
Pharmacokinetics
Metabolites
formic acid
Filarial Elephantiasis
Plasma (human)
Electrospray ionization
Monitoring
Drug Monitoring
Solid Phase Extraction
Liquid chromatography
Ion sources
Tandem Mass Spectrometry
Liquid Chromatography
Pharmaceutical Preparations
Mass spectrometry
Methanol
Clinical Studies

Keywords

  • Albendazole
  • Albendazole sulfoxide
  • Diethylcarbamazine
  • LC–MS/MS

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

Cite this

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title = "LC–MS/MS method for simultaneous determination of diethylcarbamazine, albendazole and albendazole metabolites in human plasma: Application to a clinical pharmacokinetic study",
abstract = "Combination therapy with anti-filarial drugs is now widely used for treatment of lymphatic filariasis. A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) method was developed and validated for simultaneous quantitation of diethylcarbamazine (DEC), albendazole (ABZ) and albendazole metabolites in human plasma. Separation and detection of analytes were achieved on a reversed phase column (Acquity UPLC{\circledR}BEH C18 column (100 × 2.1 mm, 1.7 μm) with gradient elution using 0.05{\%} formic acid in methanol and 0.05{\%} formic acid as mobile phase. Solid phase extraction was utilized for elution of analytes from the matrix. Thereafter, analytes were monitored by using MS/MS with electrospray ionization source in positive multiple reaction monitoring mode. The MS/MS response was linear over the concentration range from 0.1–200 ng/mL for ABZ and ABZ-ON, 0.5–1000 ng/mL for ABZ-OX and 1–2000 ng/mL for DEC with a correlation coefficient (r2) of 0.998 or better. The within- and between-batch precisions (relative standard deviation, {\%} RSD) and the accuracy ({\%} bias) were within the acceptable limits as per FDA guideline. The validated method was successfully applied to the clinical pharmacokinetic study. Due to high sensitivity and low requirement of sample volume, the method will be applicable for therapeutic drug monitoring of this regimen.",
keywords = "Albendazole, Albendazole sulfoxide, Diethylcarbamazine, LC–MS/MS",
author = "Chhonker, {Yashpal S.} and Constant Edi and Murry, {Daryl J}",
year = "2018",
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day = "20",
doi = "10.1016/j.jpba.2017.12.037",
language = "English (US)",
volume = "151",
pages = "84--90",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
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TY - JOUR

T1 - LC–MS/MS method for simultaneous determination of diethylcarbamazine, albendazole and albendazole metabolites in human plasma

T2 - Application to a clinical pharmacokinetic study

AU - Chhonker, Yashpal S.

AU - Edi, Constant

AU - Murry, Daryl J

PY - 2018/3/20

Y1 - 2018/3/20

N2 - Combination therapy with anti-filarial drugs is now widely used for treatment of lymphatic filariasis. A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) method was developed and validated for simultaneous quantitation of diethylcarbamazine (DEC), albendazole (ABZ) and albendazole metabolites in human plasma. Separation and detection of analytes were achieved on a reversed phase column (Acquity UPLC®BEH C18 column (100 × 2.1 mm, 1.7 μm) with gradient elution using 0.05% formic acid in methanol and 0.05% formic acid as mobile phase. Solid phase extraction was utilized for elution of analytes from the matrix. Thereafter, analytes were monitored by using MS/MS with electrospray ionization source in positive multiple reaction monitoring mode. The MS/MS response was linear over the concentration range from 0.1–200 ng/mL for ABZ and ABZ-ON, 0.5–1000 ng/mL for ABZ-OX and 1–2000 ng/mL for DEC with a correlation coefficient (r2) of 0.998 or better. The within- and between-batch precisions (relative standard deviation, % RSD) and the accuracy (% bias) were within the acceptable limits as per FDA guideline. The validated method was successfully applied to the clinical pharmacokinetic study. Due to high sensitivity and low requirement of sample volume, the method will be applicable for therapeutic drug monitoring of this regimen.

AB - Combination therapy with anti-filarial drugs is now widely used for treatment of lymphatic filariasis. A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) method was developed and validated for simultaneous quantitation of diethylcarbamazine (DEC), albendazole (ABZ) and albendazole metabolites in human plasma. Separation and detection of analytes were achieved on a reversed phase column (Acquity UPLC®BEH C18 column (100 × 2.1 mm, 1.7 μm) with gradient elution using 0.05% formic acid in methanol and 0.05% formic acid as mobile phase. Solid phase extraction was utilized for elution of analytes from the matrix. Thereafter, analytes were monitored by using MS/MS with electrospray ionization source in positive multiple reaction monitoring mode. The MS/MS response was linear over the concentration range from 0.1–200 ng/mL for ABZ and ABZ-ON, 0.5–1000 ng/mL for ABZ-OX and 1–2000 ng/mL for DEC with a correlation coefficient (r2) of 0.998 or better. The within- and between-batch precisions (relative standard deviation, % RSD) and the accuracy (% bias) were within the acceptable limits as per FDA guideline. The validated method was successfully applied to the clinical pharmacokinetic study. Due to high sensitivity and low requirement of sample volume, the method will be applicable for therapeutic drug monitoring of this regimen.

KW - Albendazole

KW - Albendazole sulfoxide

KW - Diethylcarbamazine

KW - LC–MS/MS

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