Determination of the rifamycin antibiotics rifabutin, rifampin, rifapentine and their major metabolites in human plasma via simultaneous extraction coupled with LC/MS/MS

Lee C. Winchester, Anthony T Podany, Joshua S. Baldwin, Brian L. Robbins, Courtney V Fletcher

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

A novel assay using high pressure liquid chromatography (HPLC) coupled to mass spectrometer (MS) detection was developed and validated for the rifamycin anti-tuberculosis antibiotics rifampicin (RIF), rifabutin (RBT), rifapentine (RPT) and their active desacetyl metabolites (dRIF, dRBT and dRPT, respectively) in human plasma. The assay uses 50. μL of human plasma with a quick and simple protein-precipitation extraction to achieve a dynamic range of 75-30,000. ng/mL for RIF, RBT and RPT and 37.5-15,000. ng/mL for dRIF, dRBT and dRPT, respectively. The average %CV and %deviation were less than 20% at the lower limit of quantitation and less than 15% over the range of the curve. The method was fully validated according to FDA criteria for bioanalytical assays and has successfully been used to support three large international tuberculosis trials.

Original languageEnglish (US)
Pages (from-to)55-61
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume104
DOIs
StatePublished - Feb 1 2015

Fingerprint

rifapentine
Rifabutin
Plasma (human)
Mass spectrometers
Rifampin
Metabolites
Assays
Tuberculosis
Anti-Bacterial Agents
High pressure liquid chromatography
High Pressure Liquid Chromatography
Proteins
rifamycin SV

Keywords

  • Bioanalysis
  • Rifabutin
  • Rifampin
  • Rifapentine
  • Tuberculosis

ASJC Scopus subject areas

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

Cite this

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title = "Determination of the rifamycin antibiotics rifabutin, rifampin, rifapentine and their major metabolites in human plasma via simultaneous extraction coupled with LC/MS/MS",
abstract = "A novel assay using high pressure liquid chromatography (HPLC) coupled to mass spectrometer (MS) detection was developed and validated for the rifamycin anti-tuberculosis antibiotics rifampicin (RIF), rifabutin (RBT), rifapentine (RPT) and their active desacetyl metabolites (dRIF, dRBT and dRPT, respectively) in human plasma. The assay uses 50. μL of human plasma with a quick and simple protein-precipitation extraction to achieve a dynamic range of 75-30,000. ng/mL for RIF, RBT and RPT and 37.5-15,000. ng/mL for dRIF, dRBT and dRPT, respectively. The average {\%}CV and {\%}deviation were less than 20{\%} at the lower limit of quantitation and less than 15{\%} over the range of the curve. The method was fully validated according to FDA criteria for bioanalytical assays and has successfully been used to support three large international tuberculosis trials.",
keywords = "Bioanalysis, Rifabutin, Rifampin, Rifapentine, Tuberculosis",
author = "Winchester, {Lee C.} and Podany, {Anthony T} and Baldwin, {Joshua S.} and Robbins, {Brian L.} and Fletcher, {Courtney V}",
year = "2015",
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doi = "10.1016/j.jpba.2014.11.011",
language = "English (US)",
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pages = "55--61",
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T1 - Determination of the rifamycin antibiotics rifabutin, rifampin, rifapentine and their major metabolites in human plasma via simultaneous extraction coupled with LC/MS/MS

AU - Winchester, Lee C.

AU - Podany, Anthony T

AU - Baldwin, Joshua S.

AU - Robbins, Brian L.

AU - Fletcher, Courtney V

PY - 2015/2/1

Y1 - 2015/2/1

N2 - A novel assay using high pressure liquid chromatography (HPLC) coupled to mass spectrometer (MS) detection was developed and validated for the rifamycin anti-tuberculosis antibiotics rifampicin (RIF), rifabutin (RBT), rifapentine (RPT) and their active desacetyl metabolites (dRIF, dRBT and dRPT, respectively) in human plasma. The assay uses 50. μL of human plasma with a quick and simple protein-precipitation extraction to achieve a dynamic range of 75-30,000. ng/mL for RIF, RBT and RPT and 37.5-15,000. ng/mL for dRIF, dRBT and dRPT, respectively. The average %CV and %deviation were less than 20% at the lower limit of quantitation and less than 15% over the range of the curve. The method was fully validated according to FDA criteria for bioanalytical assays and has successfully been used to support three large international tuberculosis trials.

AB - A novel assay using high pressure liquid chromatography (HPLC) coupled to mass spectrometer (MS) detection was developed and validated for the rifamycin anti-tuberculosis antibiotics rifampicin (RIF), rifabutin (RBT), rifapentine (RPT) and their active desacetyl metabolites (dRIF, dRBT and dRPT, respectively) in human plasma. The assay uses 50. μL of human plasma with a quick and simple protein-precipitation extraction to achieve a dynamic range of 75-30,000. ng/mL for RIF, RBT and RPT and 37.5-15,000. ng/mL for dRIF, dRBT and dRPT, respectively. The average %CV and %deviation were less than 20% at the lower limit of quantitation and less than 15% over the range of the curve. The method was fully validated according to FDA criteria for bioanalytical assays and has successfully been used to support three large international tuberculosis trials.

KW - Bioanalysis

KW - Rifabutin

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KW - Rifapentine

KW - Tuberculosis

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