Development and validation of a liquid chromatography-mass spectrometry assay for the determination of pyronaridine in human blood for application to clinical pharmacokinetic studies

Himanshu Naik, Paul Imming, Mark S. Schmidt, Daryl J. Murry, Lawrence Fleckenstein

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

A reliable and sensitive method for the determination of pyronaridine in human blood was developed and validated. A 0.3 ml aliquot of whole blood was extracted using liquid-liquid extraction after addition of amodiaquine as an internal standard. Analysis was performed on a Shimadzu LCMS-2010A in single ion monitoring positive mode using atmospheric pressure chemical ionization (APCI) as an interface. The extracted ion for pyronaridine was m/z 518.20 and for amodiaquine was m/z 356.10. Separation was achieved on a Gemini 5 μm C18 3.0 × 150 mm column using a mobile phase composed of 2 mM perflurooctanoic acid-acetonitrile mixture delivered at a flow rate of 0.5 mL/min. The mobile phase was delivered in gradient mode. The retention times of pyronaridine and amodiaquine were 9.2 and 8.2 min, respectively, with a total run time of 14 min. The estimated calibration range of the method was 5.7-855 ng/mL. The analysis of quality control samples for pyronaridine at 11.4, 285, and 760 ng/mL demonstrated excellent precision with relative standard deviation of 11.1, 4.8 and 2.2%, respectively (n = 5). Recoveries at concentrations of 11.4, 285 and 760 ng/mL were all greater than 75%. No interference peaks or matrix effects were observed. This LC-MS method for the determination of pyronaridine in human blood has excellent specifications for sensitivity, reproducibility and accuracy. This LC-MS technique was found to improve the quantitation of pyronaridine in whole blood allowing its use in pharmacokinetic studies with clinically relevant doses.

Original languageEnglish (US)
Pages (from-to)112-119
Number of pages8
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume45
Issue number1
DOIs
StatePublished - Sep 21 2007

Fingerprint

Pharmacokinetics
Liquid chromatography
Liquid Chromatography
Mass spectrometry
Assays
Mass Spectrometry
Blood
Amodiaquine
Ions
Liquid-Liquid Extraction
Atmospheric Pressure
Liquids
Quality Control
Calibration
Atmospheric pressure
Ionization
Quality control
pyronaridine
Clinical Studies
Flow rate

Keywords

  • Antimalarial
  • Liquid chromatography-mass spectroscopy
  • Pyronaridine

ASJC Scopus subject areas

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

Cite this

Development and validation of a liquid chromatography-mass spectrometry assay for the determination of pyronaridine in human blood for application to clinical pharmacokinetic studies. / Naik, Himanshu; Imming, Paul; Schmidt, Mark S.; Murry, Daryl J.; Fleckenstein, Lawrence.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 45, No. 1, 21.09.2007, p. 112-119.

Research output: Contribution to journalArticle

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abstract = "A reliable and sensitive method for the determination of pyronaridine in human blood was developed and validated. A 0.3 ml aliquot of whole blood was extracted using liquid-liquid extraction after addition of amodiaquine as an internal standard. Analysis was performed on a Shimadzu LCMS-2010A in single ion monitoring positive mode using atmospheric pressure chemical ionization (APCI) as an interface. The extracted ion for pyronaridine was m/z 518.20 and for amodiaquine was m/z 356.10. Separation was achieved on a Gemini 5 μm C18 3.0 × 150 mm column using a mobile phase composed of 2 mM perflurooctanoic acid-acetonitrile mixture delivered at a flow rate of 0.5 mL/min. The mobile phase was delivered in gradient mode. The retention times of pyronaridine and amodiaquine were 9.2 and 8.2 min, respectively, with a total run time of 14 min. The estimated calibration range of the method was 5.7-855 ng/mL. The analysis of quality control samples for pyronaridine at 11.4, 285, and 760 ng/mL demonstrated excellent precision with relative standard deviation of 11.1, 4.8 and 2.2{\%}, respectively (n = 5). Recoveries at concentrations of 11.4, 285 and 760 ng/mL were all greater than 75{\%}. No interference peaks or matrix effects were observed. This LC-MS method for the determination of pyronaridine in human blood has excellent specifications for sensitivity, reproducibility and accuracy. This LC-MS technique was found to improve the quantitation of pyronaridine in whole blood allowing its use in pharmacokinetic studies with clinically relevant doses.",
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