Abstract: AIM: To establish a HPLCQqQMS with multiple reaction monitoring (MRM) method for pharmacokinetics and tissue distribution study of ribavirin by oral and respiratory administration.  METHODS: The experiment established a highsensitivity LCMS analytical method for the detection of ribavirin, and the linearity, specificity, recovery, accuracy, and precision were investigated. The established methods were used to investigate the pharmacokinetics and tissue distribution of the oral and respiratory administration methods. RESULTS: The concentration of drugs in the blood through respiratory tract administration is higher, and the drug absorption is faster. Respiratory tract administration Cmax(46.1±10.6) μg/L and AUC(0t)(276±68) μg·L1·h are significantly higher than oral administration Cmax(8.9±3.8) μg/L and AUC(0t)(142±63) μg·L1·h. The tissue distribution results showed that the content of ribavirin in lung tissue of respiratory tract administration was significantly higher than that of oral administration, and the metabolism time was longer.CONCLUSION: Compared with oral administration, respiratory tract administration has higher blood drug concentration and higher content in lung tissue, revealing the tissue targeting effect of inhaled administration. The HPLCQqQMS detection method is simple, effective, accurate, and reproducible, which can be applied to the determination of ribavirin in rat plasma and tissue.

Key words: ribavirin, acyclovir, HPLC-QqQ-MS, ESI, tissue distribution, pharmacokinetics