Optimization of an HPLC-PDA analytical method for therapeutic monitoring of oral busulfan in hematopoietic stem cell transplant patients
Keywords:Busulfan; HPLC; Therapeutic drug monitoring.
The study aims to develop activities for therapeutic monitoring of oral busulfan in patients undergoing heterologous stem-cell transplantation (HSCT) through the identification and determination of plasma busulfan. It was used HPLC-PDA Shimadzu C18 column (150 mm x 4 mm), methanol/water/acetonitrile (65:20:15, v/v/v), flow rate 1 mL min-1, UV λ=276 nm, analysis time 17 min; derivatization with sodium diethylcarbamate, extraction with ethyl acetate; linear calibration curve over the range of 200-5000 ng ml-1. The average relative recovery of the controls was 89% ± 0.04 (QCH=86%; QCM=87%; QCL=93%), and the internal standard (IS) was 74%±0.47. The mean absolute recovery of the controls was 114±0.03% (QCH=111%, QCM=118%; QCL=113%), and the IS was 102±2.5%. The lower limits of detection and quantification obtained were respectively 200 ng ml-1 and 40 ng.mL-1. The linearity was evaluated by calibration curve (200-5000 ng.mL-1) (r=0.998, r=0.994, r=0.998). The repeatability (intracorrida) resulted in 1.25% -11.25% and intermediate precision (intercorrida) resulted in 2.17% -10.71%. The accuracy was found to be 89.61% -102.18%. The short-term stability of the solutions and samples extracted was 6.25% and 3.18% for QCL, 7.54% and 2.4% for QCH, and 4.13% and 13.17% for IS, respectively. The stability of freeze-thaw cycles extracted samples and the solutions was 3.64% and 2.53% for QCL, 9.09% and 5.65% and QCH to 4.82% and 10.32% for IS, respectively. It was concludefd that it was possible to describe a technique for determining the busulfan in plasma by HPLC-PDA, settling their validation parameters for therapeutic drug monitoring purposes.
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Copyright (c) 2021 Cristiane Effting; Fernando Gomes Ferreira Oliveira; Iram Moreira Mundim; Alessandro de Carvalho Cruz; Andryne Rego Rodrigues; Caroline Rego Rodrigues; Jerônimo Raimundo de Oliveira-Neto; Marianna Medeiros Barros da Cunha; Adriano de Moraes Arantes; Luiz Carlos da Cunha
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