| Hainanmycin is a polyether antibiotic,which was widely used for the prevention and treatment of chicken coccidiosis with intellectual property rights in China.It is currently used to control coccidiosis in livestock and poultry,especially in the case of chicken coccidia resistance to existing anticoccidial drugs,the effect of Hainanmycin is particularly significant.In order to obtain pharmacokinetic parameters,chickens were injected Hainanmycin injection or administered orally with Hainanmycin sodium premix.The pharmacokinetic process and bioavailability of Hainanmycin in chicken were used to provide a theoretical basis for developing a reasonable dosage regimen and reducing adverse reaction effectively.This study has important practical significance for enriching the clinical pharmacology of domestic veterinary drugs.1.Determination of hainanmycin in chicken plasma by HPLC-MS/MSSelecting the ESI ionization mode,and the prepared mass spectrometry tuning solution was injected through a mass spectrometer needle pump constant flow mode.Performing a Q1 scan to first determine the parent ion of the target analyte.The product ions of Hainanmycin were then determined by Product Ion Scan,and the mass-to-charge ratio scanning range was m/z 600-1000.According to the quantitative analysis procedure,the parent ion of Hainanmycin is m/z 907.6,and the daughter ions are m/z 863.6 and m/z 845.6.The optimized CE was 32.0 eV,CXP was 12.0 V,and EP was 10.0 V.Hainanmycin in chicken plasma is extracted by liquid-liquid extraction.Various components in the sample were separated using an Ultimate UHPLC XB-C18(1.8 ?m,2.1 × 100 mm)column and isocratic elution.An external standard method of quantitative analysis was performed using a multiple reaction monitoring mode of a triple quadrupole mass spectrometer.Mobile phase A was acetonitrile,B was 0.1%aqueous formic acid(containing 5 mmol/L ammonium acetate),the flow rate was 0.4 mL/min,and the injection volume was 5 ?L.Under selected chromatographic conditions,Hainanmycin showed a good linear relationship in the concentration range of 1-500 ng/mL,and the correlation coefficient was greater than 0.999.The limit of detection(LOD)and limit of quantity(LOQ)of this method were 0.5 ng/mL and 1 ng/mL.The inter-assay recovery rates of high,medium and low blank plasma samples(1,100,500 ng/mL)were 95.6±6.36%,101.6±5.78%,94.0±5.88%,and the intra-day coefficient of variation were 5.42-7.65%,4.94-6.22%and 5.44-6.80%,the daytime coefficient of variation was 5.70%-6.66%.The results showed that the established method for the extraction and determination of Hainanmycin in chicken plasma was highly specific.Besides,the matrix effect was not obvious.The analyte in the standard stock solution and tested sample had high stability under given conditions.The optimized HPLC-MS/MS method was successfully applied for the determination of Hainanmycin in chicken plasma.2.Study on the pharmacokinetics and bioavailability of Hainanmycin in chickenSixteen healthy AA chickens(average weight:3 ± 0.51 kg)were randomly divided into 2 groups of 8 animals each.Pharmacokinetic studies of oral and intravenous administration were performed using a parallel test design.A single dose of 1.5 mg/kg bw Hainanmycin was administrated to group 1 via oral.A single dose of 1.5 mg/kg bw Hainanmycin was administrated to group 2 via Intravenous injection.All chickens were fasting for 12 hours before administration and started normal drinking again after 2 hours of administration.Blood samples were taken at predetermined time points.The content of Hainanmycin in plasma was analyzed by HPLC-MS/MS triple quadrupole detector.The mobile phase was acetonitrile-0.1%aqueous formic acid(90:10,V/V).The measured blood concentration-time data of Hainanmycin was calculated using Winnonlin 5.2 pharmacokinetic analysis softwarePharmacokinetic results showed that the mean elimination half-life(T1/2)of the oral administration group was 28.07 h and the mean residence time(MRT)was 8.40 h.The peak time(Tmax)in plasma was about 0.5 h,and the peak concentrations(Cmax)was about 68.88 ng/mL The area under the mean time curve of 0-24h(AUC0-24 h)was 307.23 ng·h/mL.The mean bioavailability(FO-24h)estimated by AUC0-24h was 16.97%.The mean elimination half-life(T1/2)and mean residence time(MRT)of the single-dose intravenous group were approximately 46.32 h and 3.31 h,and the mean plasma clearance(CL)was 0.58 L/(kg·h),with an average appearance.The distribution volume(Vd)is approximately 35.52 L/kgThe results showed that the absorbtion of Hainanmycin after oral administration was rapid,but incomplete.Hainanmycin was widely distributed after entering the chicken body,and the elimination was slow and the mean elimination half-life(T1/2)was long. |
PDF Full Text Request