| Marbofloxacin?MBX?,a new type of fluoroquinolone antibacterial drugs,was created by Roche Group.It was listing in the UK in 1995 through further developed by Vetoquinol S.A.,and was listed as animal-specific drugs in France,the United States and Europe,FDA approves it for companion animals such as dogs and cats.MBF which has wide antimicrobial spectrum,high bioavailability,can inhibit the growth of bacteria by inhibiting the bacterial DNA gyrase and topoisomerase IV.After oral and intravenous injection,it can be absorbed quickly and completely,It has many advantages such as lower binding rate of plasma protein,widely distributed in the organization of body,including kidney,liver,lungs and skin.The concentration of plasma and tissue is higher than the minimum inhibitory concentration?MIC?of the pathogen.In clinical,It has been used in treatment of dog and cat infections,such as skin includes superficial and deep,urinary tract,gastrointestinal and upper respiratory tract infection.With the development of the domestic pet market,drugs for pet were shortage.MBX have good antibacterial activity,broad spectrum,lower binding rate of plasma protein and wide distribution of organizations.So we do some rearch on MBX in order to solve some problem on pet.The purpose of the research was to make marbofloxacin tablets like product which produced in Vetoquinol Company,As well,To establish a high performance liquid chromatography-tandem mass spectrometry?HPLC-MS/MS?method for the determination of MBX in poodle plasma between test sample and reference product,then to evaluate its bioequivalence.And if it's successful,we can solve the problem like higher price in domestic pet drugs,shortage of pet drugs,and helpful in treatment of bacterial infections caused by some diseases of dogs and cats,Then improve the level of domestic pet health.In order to solve the problem of pet feeding,this study aims to improve the palatability of Marbofloxacin tablets,through orthogonal test to screen out the best ratio of excipients and main materials.Marbofloxacin tablets uniformity,palatability,dissolution and content as an evaluation index,with dissolution tester high-performance liquid chromatography?HPLC?to detect the content of MBX.The results showed that the main drug content was 5%.Using the sodium carboxymethyl starch the disintegrating agent,and tablet by both inside and outside pressure,with the perusal to observation tablets surface gloss and form ability,with dissolution tester and UV spectrophotometry to measure dissolution,with high performance liquid chromatography to measure content,under the optimal ratio condition,Our result showed that the optimal palatability condition is 5%of the main drug in each tablet,and the dissolution of Marbofloxacin was100.23%and the average content of each tablet was 100.16%.Therefore,using this method to prepare Marbofloxacin tablet is more effectively,and the content and uniformity conforms to the requirement of national veterinary drug standard with higher palatability in comparison with the competing drug,Marbofloxacin.Established a high performance liquid chromatography-tandem mass spectrometry method to detection the MBX in poodle plasma between test sample and reference product,then to evaluate its bioequivalence.The beagle plasma samples were applied to a luna 5?m C18 interfaced with a tripple quadrupole tandem mass spectrometer after pretreated with acetonitrile,centrifugate 12000 rpm for 10 min at 4?,get supernatant dry in nitrogen blowing machine at 50?,Redissolve with mobile phases,acetonitrile?phase A?and water?phaseB?both containing 0.1%formic acid?A:B=20:80v/v?;positive electrospray ionization was employed as the ionzation source,The analyte and IS ofloxacin were detected by the use of multiple reaction monitoring?MRM?.The method was linear in the concentration range of 1-250 ng·mL-11 for plasma marbofloxacin samples,with the average extraction recovery rate of the Marbofloxacin was 101.28±0.14;99.42±3.14;101.84±1.74;100.02±0.47 respectively.The relative standard deviation was no more than 3.0%.The established quantitative analysis method conforms to the guidelines of biological sample analysis,and it can be applied to evaluate the pharmacokinetics of marbofloxacin.The experiment also does some research on Pharmacokinetics of Marbofloxacin in dogs after single oral administration.The weight of the selected poodle dog was 5-8kg,and the dosage was 2 mg/kg.Analyze the pharmacokinetic parameters was carried by Winnonlin5.2 software.The test sample and reference product pharmacokinetic para-meters results are as follows:AUC were 10.71±1.38 mg·h·L-11 and 10.68±1.31 mg·h·L-1,peak time was 2.13±0.54 h and 2.13±0.54 h,maximal concentration was 0.86±0.10mg·L-1and 0.88±0.10 mg·L-1.And the maximal concentration and the peak time of test sample were similar to the reference product,AUC between 80%and 120%for the test sample,so test samples and reference products bio-equivalent.In conclusion,our test samples is not only convenient to administration,easy to product,lower cost,smooth surface without spots,good stability.But bio-equivalent to reference product.The area under the curve of the test samples were between 80%and120%,accord with China Phannacopeia 2015. |
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