RESUMEN
Aims: To validate an SPE-ultra-HPLC-MS/MS method for thalidomide (THD) measurement in dried plasma spot (DPS). Methods: Extraction included acetonitrile/water clean-up and online SPE. The LOD, LLOQ, linearity, precision, accuracy, recovery, matrix effect, process efficiency, carryover, stability, drug interference and dilution integrity were assessed. Results: The method was linear from 50 to 2000 ng/ml with a LOD of 20 ng/ml and LLOQ of 50 ng/ml. The coefficient of variation for precision was 0.4-7.9% for intra-assay and 1.3-8.9% for interassay, and accuracy was 81.4-97.1%. Adequate matrix effect (100.6-107.0%), recovery (88.7-105.0%) and process efficiency (91.3-109.3%) were registered. DPS was stable for 14 days at room temperature and 45°C ,and for 4 months at -80°C. The method was applied to quantify THD in both wet plasma and DPS from patients with cutaneous lupus receiving THD treatment. The difference between THD wet plasma and DPS concentration was <15%. Conclusion: The method is suitable to quantify THD in DPS.
Asunto(s)
Monitoreo de Drogas , Espectrometría de Masas en Tándem , Acetonitrilos , Cromatografía Líquida de Alta Presión/métodos , Pruebas con Sangre Seca/métodos , Monitoreo de Drogas/métodos , Humanos , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/métodos , Talidomida , AguaRESUMEN
BACKGROUND AND OBJECTIVES: Elderly patients are increasingly likely to be recipients of transplants. However, the pharmacokinetics of mycophenolic acid (MPA) in this population are yet to be studied in detail. The objective of this study was to assess whether there were differences in MPA pharmacokinetic parameter values between elderly recipients and younger-adult recipients during the 6 months immediately following renal transplantation. METHODS: In this analysis, the longitudinal 12-h pharmacokinetics of MPA, administered as enteric-coated mycophenolate sodium (EC-MPS), were evaluated in 44 elderly renal transplant recipients and compared with the corresponding pharmacokinetics of MPA in 31 younger adult recipients. Measurements were performed at 7, 30, 60, 90, and 180 days post-transplantation. All patients received tacrolimus and prednisone. RESULTS: The elderly patients were 30 years older than the younger controls, with a predominance of males and Caucasians. Elderly patients had lower serum albumin than the younger controls during the first 6 months after transplantation. The mean estimated total body MPA clearance of the elderly recipients was not significantly different from that of the controls at any analyzed time point (the mean clearance across all time points was 0.31 ± 0.17 vs 0.30 ± 0.25 L/h/kg). MPA exposure, as evaluated from the area under the 12-h time versus measured MPA concentration (adjusted for dose/body weight) curve, did not differ between the groups at any time point (mean exposure across all time points was 4.68 ± 3.61 vs 5.95 ± 4.29 µg·h/mL per mg/kg for the elderly recipients and the controls). CONCLUSIONS: These data show that the pharmacokinetics of MPA in elderly renal transplant recipients were no different to those of younger-adult recipients in this study population. CLINICALTRIALS.GOV: NCT 01631058.