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

@article{33d6984b762e4adda95f2dd1ea39807b,
title = "Development and validation of a liquid chromatography-mass spectrometry assay for the determination of pyronaridine in human blood for application to clinical pharmacokinetic studies",
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.",
keywords = "Antimalarial, Liquid chromatography-mass spectroscopy, Pyronaridine",
author = "Himanshu Naik and Paul Imming and Schmidt, {Mark S.} and Murry, {Daryl J} and Lawrence Fleckenstein",
year = "2007",
month = "9",
day = "21",
doi = "10.1016/j.jpba.2007.06.018",
language = "English (US)",
volume = "45",
pages = "112--119",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
issn = "0731-7085",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Development and validation of a liquid chromatography-mass spectrometry assay for the determination of pyronaridine in human blood for application to clinical pharmacokinetic studies

AU - Naik, Himanshu

AU - Imming, Paul

AU - Schmidt, Mark S.

AU - Murry, Daryl J

AU - Fleckenstein, Lawrence

PY - 2007/9/21

Y1 - 2007/9/21

N2 - 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.

AB - 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.

KW - Antimalarial

KW - Liquid chromatography-mass spectroscopy

KW - Pyronaridine

UR - http://www.scopus.com/inward/record.url?scp=34548514014&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548514014&partnerID=8YFLogxK

U2 - 10.1016/j.jpba.2007.06.018

DO - 10.1016/j.jpba.2007.06.018

M3 - Article

VL - 45

SP - 112

EP - 119

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

IS - 1

ER -