Comparison of Two Analytical Methods for Busulfan Therapeutic Drug Monitoring

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 AUC_0–∞] 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.