Development and validation of an LC–MS/MS method for the simultaneous quantification of milbemycin oxime and praziquantel in plasma: application to a pharmacokinetic study in cats

IntroductionMilbemycin oxime (MBO) and praziquantel (PZQ) have a broad spectrum of biological activity and are commonly used to treat the parasitic infection in the veterinary clinic. In this study, a fast and efficient LC-MS/MS method was established and validated for the simultaneous determination...

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Main Authors: Shiting Xie, Yixing Lu, Jun Wang, Changcheng Lin, Peiyu Ye, Xiaolin Liu, Wenguang Xiong, Zhenling Zeng, Dongping Zeng
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-10-01
Series:Frontiers in Veterinary Science
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fvets.2023.1285932/full
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author Shiting Xie
Shiting Xie
Yixing Lu
Yixing Lu
Jun Wang
Jun Wang
Changcheng Lin
Changcheng Lin
Peiyu Ye
Peiyu Ye
Xiaolin Liu
Wenguang Xiong
Wenguang Xiong
Zhenling Zeng
Zhenling Zeng
Dongping Zeng
Dongping Zeng
author_facet Shiting Xie
Shiting Xie
Yixing Lu
Yixing Lu
Jun Wang
Jun Wang
Changcheng Lin
Changcheng Lin
Peiyu Ye
Peiyu Ye
Xiaolin Liu
Wenguang Xiong
Wenguang Xiong
Zhenling Zeng
Zhenling Zeng
Dongping Zeng
Dongping Zeng
author_sort Shiting Xie
collection DOAJ
description IntroductionMilbemycin oxime (MBO) and praziquantel (PZQ) have a broad spectrum of biological activity and are commonly used to treat the parasitic infection in the veterinary clinic. In this study, a fast and efficient LC-MS/MS method was established and validated for the simultaneous determination of MBO, PZQ, cis-4-hydroxylated-PZQ (C-4-OH-PZQ) and trans-4-hydroxylated-PZQ (T-4-OH-PZQ) and in cat plasma.MethodsExtraction of analytes and internal standards from cat plasma by acetonitrile protein precipitation, allows rapid processing of large batches of samples. MBO, PZQ, C-4-OH-PZQ, T-4-OH-PZQ, and internal standard (IS) were eluted for 13.5 min on a C18 column with a 0.1% formic acid water/acetonitrile mixture as the mobile phase.ResultsResults showed that the method had good precision, accuracy, recovery, and linearity. The linearity range was 2.5–250 ng/mL for MBO, and 10–1000 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ. The intra-day and inter-day precision CV values of the tested components were within 15%. The extraction recoveries of the four components ranged from 98.09% to 107.46%. The analytes in plasma remained stable for 6 h at room temperature, 26 h in the autosampler (4 °C), after freeze–thaw (−20°C) cycles, and 60 days in a −20°C freezer. Method sensitivity sufficed for assessing pharmacokinetic parameters of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in plasma samples with LLOQ of 2.5 ng/mL for MBO and 10 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ.ConclusionIn this study, a selective and sensitive LC-MS/MS method for the simultaneous quantification of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in cat plasma was developed and validated.This method had been successfully applied to evaluate the pharmacokinetics of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ after a single oral administration of 8 mg MBO and 20 mg PZQ in cats.
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spelling doaj.art-c28a7b2d8ed647e8b36de42092b973dd2023-10-30T05:17:46ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692023-10-011010.3389/fvets.2023.12859321285932Development and validation of an LC–MS/MS method for the simultaneous quantification of milbemycin oxime and praziquantel in plasma: application to a pharmacokinetic study in catsShiting Xie0Shiting Xie1Yixing Lu2Yixing Lu3Jun Wang4Jun Wang5Changcheng Lin6Changcheng Lin7Peiyu Ye8Peiyu Ye9Xiaolin Liu10Wenguang Xiong11Wenguang Xiong12Zhenling Zeng13Zhenling Zeng14Dongping Zeng15Dongping Zeng16Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, Guangzhou, ChinaLivcare (Guangdong) Animal Health Co., Ltd, Qingyuan, ChinaGuangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, Guangzhou, ChinaIntroductionMilbemycin oxime (MBO) and praziquantel (PZQ) have a broad spectrum of biological activity and are commonly used to treat the parasitic infection in the veterinary clinic. In this study, a fast and efficient LC-MS/MS method was established and validated for the simultaneous determination of MBO, PZQ, cis-4-hydroxylated-PZQ (C-4-OH-PZQ) and trans-4-hydroxylated-PZQ (T-4-OH-PZQ) and in cat plasma.MethodsExtraction of analytes and internal standards from cat plasma by acetonitrile protein precipitation, allows rapid processing of large batches of samples. MBO, PZQ, C-4-OH-PZQ, T-4-OH-PZQ, and internal standard (IS) were eluted for 13.5 min on a C18 column with a 0.1% formic acid water/acetonitrile mixture as the mobile phase.ResultsResults showed that the method had good precision, accuracy, recovery, and linearity. The linearity range was 2.5–250 ng/mL for MBO, and 10–1000 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ. The intra-day and inter-day precision CV values of the tested components were within 15%. The extraction recoveries of the four components ranged from 98.09% to 107.46%. The analytes in plasma remained stable for 6 h at room temperature, 26 h in the autosampler (4 °C), after freeze–thaw (−20°C) cycles, and 60 days in a −20°C freezer. Method sensitivity sufficed for assessing pharmacokinetic parameters of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in plasma samples with LLOQ of 2.5 ng/mL for MBO and 10 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ.ConclusionIn this study, a selective and sensitive LC-MS/MS method for the simultaneous quantification of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in cat plasma was developed and validated.This method had been successfully applied to evaluate the pharmacokinetics of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ after a single oral administration of 8 mg MBO and 20 mg PZQ in cats.https://www.frontiersin.org/articles/10.3389/fvets.2023.1285932/fullmilbemycin oximepraziquantelLC–MS/MScat plasmapharmacokinetics
spellingShingle Shiting Xie
Shiting Xie
Yixing Lu
Yixing Lu
Jun Wang
Jun Wang
Changcheng Lin
Changcheng Lin
Peiyu Ye
Peiyu Ye
Xiaolin Liu
Wenguang Xiong
Wenguang Xiong
Zhenling Zeng
Zhenling Zeng
Dongping Zeng
Dongping Zeng
Development and validation of an LC–MS/MS method for the simultaneous quantification of milbemycin oxime and praziquantel in plasma: application to a pharmacokinetic study in cats
Frontiers in Veterinary Science
milbemycin oxime
praziquantel
LC–MS/MS
cat plasma
pharmacokinetics
title Development and validation of an LC–MS/MS method for the simultaneous quantification of milbemycin oxime and praziquantel in plasma: application to a pharmacokinetic study in cats
title_full Development and validation of an LC–MS/MS method for the simultaneous quantification of milbemycin oxime and praziquantel in plasma: application to a pharmacokinetic study in cats
title_fullStr Development and validation of an LC–MS/MS method for the simultaneous quantification of milbemycin oxime and praziquantel in plasma: application to a pharmacokinetic study in cats
title_full_unstemmed Development and validation of an LC–MS/MS method for the simultaneous quantification of milbemycin oxime and praziquantel in plasma: application to a pharmacokinetic study in cats
title_short Development and validation of an LC–MS/MS method for the simultaneous quantification of milbemycin oxime and praziquantel in plasma: application to a pharmacokinetic study in cats
title_sort development and validation of an lc ms ms method for the simultaneous quantification of milbemycin oxime and praziquantel in plasma application to a pharmacokinetic study in cats
topic milbemycin oxime
praziquantel
LC–MS/MS
cat plasma
pharmacokinetics
url https://www.frontiersin.org/articles/10.3389/fvets.2023.1285932/full
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