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. 2024 Oct 10;29(20):4786.
doi: 10.3390/molecules29204786.

Development of a UHPLC-MS/MS Method for the Determination of Moxidectin in Rat Plasma and Its Application in Pharmacokinetics

Hongjuan Zhang  1 , Zhen Yang  1 , Baocheng Hao  1 , Di Wu  1 , Dan Shao  1 , Yu Liu  1 , Wanxia Pu  1 , Shouli Yi  1 , Ruofeng Shang  1 , Shengyi Wang  1
Affiliations

Development of a UHPLC-MS/MS Method for the Determination of Moxidectin in Rat Plasma and Its Application in Pharmacokinetics

Hongjuan Zhang et al. Molecules. .

Abstract

The aim of the present study was to establish a simple and reliable ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method and apply it for the determination of pharmacokinetics of moxidectin-loaded microspheres (MOX-MS) in rats. Plasma samples were processed using a simplified liquid-liquid extraction method and were separated using an Agilent Zorbax Eclipse Plus C18 column (50 mm × 2.1 mm, 1.8 μm) with a mobile phase consisting of a 10 mM ammonium formate solution with 0.1% formic acid (A) and acetonitrile (B) at a flow rate of 0.4 mL/min for 5 min. Avermectin B1a was used as an internal standard (IS). The sample was injected at a volume of 10 μL with a column temperature of 35 °C and detected in a positive ion mode. A good linear response across the concentration range of 1.00-200 ng/mL (r2 > 0.99) and a lower limit of quantification (LLOQ) of 1.00 ng/mL were achieved. The extraction recovery of moxidectin exceeded 94.1%, the matrix effect was between 91.2% and 96.2%, the accuracy ranged from 100.1 to 103.6%, and the relative standard deviation (RSD) did not exceed 15% for the intra- and inter-day accuracy and precision. The pharmacokinetic results showed that MOX-MS significantly decreased Cmax, prolonged T1/2, and improved bioavailability. The developed method significantly reduced the assay volume, shortened detection time, simplified sample processing methods and saved assay costs, which may contribute to the development of the new antiparasitic drug.

Keywords: UPLC-MS/MS; microspheres; moxidectin; pharmacokinetics; rat.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Product ion spectra of moxidectin (A) and avermectin B1a (B).
Figure 2
Figure 2
Chromatograms of moxidectin and IS in rat plasma. (A) blank plasma; (B) a blank plasma spiked with LLOQ; (C) a plasma sample obtained after a single subcutaneous injection of 1 mg/kg moxidectin.
Figure 3
Figure 3
Plasma concentration–time curves of moxidectin in rats after subcutaneous administration (1 mg/kg) (n = 6). (A) Moxidectin solution; (B) Moxidectin microspheres.
See this image and copyright information in PMC

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