Bioanalytical method development and validation of moxidectin in plasma by LC–MS/MS: Application to in vitro metabolism

Yashpal S. Chhonker, Richard L. Sleightholm, Daryl J Murry

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Moxidectin (MOX) has recently been approved by the US Food and Drug Administration for the treatment of river blindness in select populations. It is also being evaluated as an alternative for the use of ivermectin, widespread resistance to which is becoming a global health issue. Moreover, MOX is becoming increasingly used as a prophylactic antiparasitic in the cattle industry. In this study, we developed and validated an LC–MS/MS method of MOX in human, monkey and mouse plasma. The separation was achieved on an ACE C 18 (50 × 3.0 mm, 3 μm) column with isocratic elution using 0.1% acetic acid and methanol–acetonitrile (1:1, v/v) as mobile phase. MOX was quantitated using MS/MS with an electrospray ionization source operating in negative multiple reaction monitoring mode. The multiple reaction monitoring precursor ion → product ion transitions for MOX and abamectin (IS) were m/z 638.40 → 236.30 and m/z 871.50 → 565.35 respectively. The MS/MS response was linear over the concentration range 0.1–1000 ng/mL in plasma with a correlation coefficient (r 2 ) of 0.997 or better. The within- and between-day precision (relative standard deviation, RSD) and accuracy were within the acceptable limits per US Food and Drug Administration guidelines. The method was successfully applied to an in vitro metabolic stability study of MOX.

Original languageEnglish (US)
Article numbere4389
JournalBiomedical Chromatography
Volume33
Issue number2
DOIs
StatePublished - Feb 1 2019

Fingerprint

Metabolism
Plasmas
abamectin
United States Food and Drug Administration
Ocular Onchocerciasis
Ions
Antiparasitic Agents
Ivermectin
Electrospray ionization
Monitoring
Ion sources
Acetic Acid
Haplorhini
milbemycin
In Vitro Techniques
Industry
Rivers
Health
Guidelines
Population

Keywords

  • LC–MS/MS
  • in-vitro metabolism
  • moxidectin

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Bioanalytical method development and validation of moxidectin in plasma by LC–MS/MS : Application to in vitro metabolism. / Chhonker, Yashpal S.; Sleightholm, Richard L.; Murry, Daryl J.

In: Biomedical Chromatography, Vol. 33, No. 2, e4389, 01.02.2019.

Research output: Contribution to journalArticle

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