LC-MS/MS法测定小型猪血浆中泰妙菌素浓度及其在不同制剂药代动力学研究中的应用OA

The present study aimed to establish an LC-MS/MS method for the quantification of tiamulin in minipig plasma and to further conduct a pharmacokinetic comparison of different formulations.The plasma samples were extracted with acetonitrile(meloxicam as internal standard),separated on a C18 column,and quantified by multiple reaction monitoring mode(ESI+).Sanyuan minipigs were used as experimental animals.Plasma samples were collected after intravenous injection(10 mg/kg)and intragastric administration(20 mg/kg).The method showed good linearity,with intra-and inter-batch RSD of 1.00%-8.13%and RE within±15%.The extraction recovery,matrix effect and stability of the analytical methods met the relevant requirements.Tiamulin fumarate active pharmaceutical ingredient was intravenously administered,with c0 of about(4 383.73±2 676.78)ng/mL,AUC0-t of about(4 803.50±965.68)h·ng/mL,t1/2 of about(4.66±1.68)h,and CL of about(2.14±0.46)L/(kg·h).Three tiamulin formulations were intragastrically administered,with cmax of(552.00±328.55),(545.00±136.97)and(590.60±237.02)ng/mL,tmax of(1.47±0.68),(0.69±0.75)and(0.72±0.72)h,and F of 24.85%,15.28%and 16.97%,respectively.The validated method meets the requirements for biological sample analysis and is applicable for the pharmacokinetic evaluation of tiamulin formulations in minipigs.