title: Development of an ultra fast liquid chromatography-tandem mass spectrometry method for simultaneous determination of cefazedone and etimicin in beagle dog plasma: Application to the pharmacokinetic study of the combination of cefazedone and etimicin injections.
abstract: A new, sensitive and efficient ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed and validated for simultaneous quantification of cefazedone and etimicin in beagle dog plasma. After addition of the internal standard (IS) metronidazole, plasma samples were treated by protein precipitation procedure, and then separated on a Venusil MP C18column (100mm×2.1mm, 3.0μm) (Venusil, China) using gradient elution with the mobile phase consisting of 0.01% heptafluorobutyric acid (HFBA) in acetonitrile and 0.01% HFBA in water at a flow rate of 0.4mLmin-1. The detection of the analytes was performed on 4000Q UFLC-MS/MS system with turbo ion spray source in the positive ion and multiple reaction-monitoring (MRM) mode. The linear range was 1.0-200μgmL-1for cefazedone and 0.5-100μgmL-1for etimicin, with lower limits of quantification of 1.0 and 0.5μgmL-1, respectively. Intra-day and inter-day precisions were within 7.2% and 4.3%, respectively for both analytes, and the accuracy (relative error, RE, %) was less than 10.7% and 12.7%, respectively. The mean absolute extraction recoveries of analytes and IS from beagle dog plasma were all more than 73.22%. The validated method was successfully applied to the pharmacokinetic study of cefazedone and etimicin in beagle dog after intravenous administration of cefazedone injection combined with etimicin injection and the two single injections alone, respectively. The results indicated there were not obvious differences between the pharmacokinetic behaviors between the combined group and either of the single groups.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; Shandong Luoxin Pharmaceutical Co., Ltd., Linyi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Liaoning Academy of Chinese Medicine, Shenyang, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Lv
authors.affiliation: Shandong Luoxin Pharmaceutical Co., Ltd., Linyi, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Li
authors.affiliation: Shandong Luoxin Pharmaceutical Co., Ltd., Linyi, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Li
authors.affiliation: Shandong Luoxin Pharmaceutical Co., Ltd., Linyi, China.
authors.forename: Liangwei
authors.initials: L
authors.lastname: Song
authors.affiliation: Shandong Luoxin Pharmaceutical Co., Ltd., Linyi, China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: kaishunbi.syphu@gmail.com.
authors.forename: Kaishun
authors.initials: K
authors.lastname: Bi
keywords: Cefazedone; Etimicin; Pharmacokinetics; Ultra fast liquid chromatography–tandem mass spectrometry