ROUTINE CLINICAL MONITORING OF SIROLIMUS (RAPAMYCIN) WHOLE-BLOOD CONCENTRATIONS BY HPLC WITH ULTRAVIOLET DETECTION

During phase I/II clinical trials of sirolimus (rapamycin; SRL), thera peutic drug monitoring was performed with a multistep liquid-liquid ex traction of 1-mL aliquots of whole blood followed by reversed-phase HP LC with ultraviolet detection. Blood was sampled according to a standa rdized protocol and clinical status. SRL concentrations were interpola ted from calibration curves with a linear range of 0-50 mu g/L and 1 m u g/L lower limit of quantification. Quality control was monitored ove r 68 consecutive analytical runs by using frozen aliquots of SRL-suppl emented pooled whole blood at 4, 12, and 32 mu g/L. These samples show ed mean concentrations of 3.7 +/- 0.6, 10.9 +/- 1.1, and 29.6 +/- 2.6 mu g/L, respectively, This method for therapeutic drug monitoring of S RL permits one full-time technician to analyze 100 clinical specimens per week with a 24-h turnaround time. With this method, a strong linea r relation (r(2) = 0.946, S-ylx = 0.41, n = 115) between the average S RL concentration over a 24-h period and the SRL concentration at the 2 4th h was revealed.