Routine clinical monitoring of sirolimus (rapamycin) whole-blood concentrations by HPLC with ultraviolet detection.
During phase I/II clinical trials of sirolimus (rapamycin; SRL), therapeutic drug monitoring was performed with a multistep liquid-liquid extraction of 1-mL aliquots of whole blood followed by reversed-phase HPLC with ultraviolet detection. Blood was sampled according to a standardized protocol and clinical status. SRL concentrations were interpolated from calibration curves with a linear range of 0-50 micrograms/L and 1 microgram/L lower limit of quantification. Quality control was monitored over 68 consecutive analytical runs by using frozen aliquots of SRL-supplemented pooled whole blood at 4, 12, and 32 micrograms/L. These samples showed mean concentrations of 3.7 +/- 0.6, 10.9 +/- 1.1, and 29.6 +/- 2.6 micrograms/L, respectively. This method for therapeutic drug monitoring of SRL permits one full-time technician to analyze 100 clinical specimens per week with a 24-h turnaround time. With this method, a strong linear relation (r2 = 0.946, Sy/x = 0.41, n = 115) between the average SRL concentration over a 24-h period and the SRL concentration at the 24th h was revealed.
Napoli
K L
KL
Department of Surgery, University of Texas Houston Health Science Center-Medical School 77030, USA. knapoli@orgtx71.med.uth.tmc.edu
Kahan
B D
BD
D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D016903:Drug Monitoring; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood*; D011090:Polyenes / Q000097:blood* / Q000493:pharmacokinetics; D011786:Quality Control; D012680:Sensitivity and Specificity; D020123:Sirolimus
D007166:Immunosuppressive Agents; D011090:Polyenes; D020123:Sirolimus