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

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 C18 (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 (r2) 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.

Moxidectin is a candidate for use as an in vivo internal standard in pharmacokinetic studies, as demonstrated with use in simultaneous tissue cage and ultrafiltration fluid collection

“…Samples were stored at 4°C prior to centrifugation, the plasma (blood) or sediment free (tissue cage) fluid was decanted into 1.5 mL microcentrifuge tubes and stored at −80°C until analysis (≤21 days). Carprofen and Moxidectin have been shown to be stable in canine and human plasma, respectively at −80°C ( 19 , 20 ).…”

Synthesis and Evaluation of Galloyl Conjugates of Flavanones as BMP-2 Upregulators with Promising Bone Anabolic and Fracture Healing Properties

“…The percentage of the analyte remaining intact at different time intervals after incubation was determined by eq , and the graph was plotted between the normal logarithmic of the compound remaining over time. , The curve slope was defined as a depletion rate constant K (min –1 ). The half-life ( t 1/2 ) and in vitro intrinsic clearance (CL ins ) were determined by eqs and , respectively. …”

“…remaining over time. 52,53 The curve slope was defined as a depletion rate constant K (min −1 ). The half-life (t 1/2 ) and in vitro intrinsic clearance (CL ins ) were determined by eqs 2 and 3, respectively.…”

Synthesis, Biological Evaluation, Structure–Activity Relationship, and Mechanism of Action Studies of Quinoline–Metronidazole Derivatives Against Experimental Visceral Leishmaniasis

“…The percentage of compound remaining intact at different time intervals after incubation was determined by the eq and the in vitro metabolic half-life ( t 1/2 ) was determined by plotting the natural logarithm of percentage compound remaining versus time. , The slope of the curve was represented as depletion rate constant K (min –1 ). The half-life of metabolic stability was estimated using the first-order eq .…”