TY - JOUR
T1 - Comparison of Two Analytical Methods for Busulfan Therapeutic Drug Monitoring
AU - De Gregori, Simona
AU - Tinelli, Carmine
AU - Manzoni, Federica
AU - Bartoli, Antonella
N1 - Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - Background and Objectives: Busulfan (Bu) is an old drug, but is still well recommended as an alkylating agent during conditioning therapy, before hematopoietic stem cell transplantation. Although its dose administration is standardized and based on patient weight, therapeutic drug monitoring is required in order to maintain its exposure [as area under the concentration-time curve (AUC) from 0 to infinity AUC0–∞] within a narrow therapeutic range and, if necessary, to adjust the dose with as short a lead time as possible. The aim of the study is to evaluate the agreement (as calculated AUC) between a gold standard analytical method and a new one that is faster and easier. Methods: We analyzed 221 plasma samples from 37 children (0.25–16 years; 4–62.5 kg) and 11 adults (21–59 years; 45–80 kg), corresponding to 52 AUC values (ng h/mL). The drug exposure was calculated, simultaneously, by two validated analytical methods. The reference method was a high-performance liquid chromatography (HPLC) assay combined with an ultraviolet detector (UV). The test method had a triple quadrupole mass spectrometer (MS) as detector; the clean-up procedures of the samples were different and faster. Results: The agreement between the two methods (reference and test) was evaluated in terms of Bu exposure differences based on Lin’s concordance correlation coefficient (CCC) and represented by the Bland–Altman plot. The CCC between the AUC of the two methods was excellent (0.868; 95% CI: 0.802–0.935). The precision of the measures (expressed by Pearson's italic "r") was 0.872, and the accuracy (accounted by the bias correction factor) was 0.996. Conclusions: We can conclude that the HPLC–MS/MS assay represents a very good alternative to the reference.
AB - Background and Objectives: Busulfan (Bu) is an old drug, but is still well recommended as an alkylating agent during conditioning therapy, before hematopoietic stem cell transplantation. Although its dose administration is standardized and based on patient weight, therapeutic drug monitoring is required in order to maintain its exposure [as area under the concentration-time curve (AUC) from 0 to infinity AUC0–∞] within a narrow therapeutic range and, if necessary, to adjust the dose with as short a lead time as possible. The aim of the study is to evaluate the agreement (as calculated AUC) between a gold standard analytical method and a new one that is faster and easier. Methods: We analyzed 221 plasma samples from 37 children (0.25–16 years; 4–62.5 kg) and 11 adults (21–59 years; 45–80 kg), corresponding to 52 AUC values (ng h/mL). The drug exposure was calculated, simultaneously, by two validated analytical methods. The reference method was a high-performance liquid chromatography (HPLC) assay combined with an ultraviolet detector (UV). The test method had a triple quadrupole mass spectrometer (MS) as detector; the clean-up procedures of the samples were different and faster. Results: The agreement between the two methods (reference and test) was evaluated in terms of Bu exposure differences based on Lin’s concordance correlation coefficient (CCC) and represented by the Bland–Altman plot. The CCC between the AUC of the two methods was excellent (0.868; 95% CI: 0.802–0.935). The precision of the measures (expressed by Pearson's italic "r") was 0.872, and the accuracy (accounted by the bias correction factor) was 0.996. Conclusions: We can conclude that the HPLC–MS/MS assay represents a very good alternative to the reference.
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U2 - 10.1007/s13318-020-00660-2
DO - 10.1007/s13318-020-00660-2
M3 - Article
C2 - 33231835
AN - SCOPUS:85096480791
VL - 46
SP - 155
EP - 159
JO - European Journal of Drug Metabolism and Pharmacokinetics
JF - European Journal of Drug Metabolism and Pharmacokinetics
SN - 0378-7966
IS - 1
ER -