Clinical and Experimental Pharmacokinetics Unit, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi, 19, 27100, Pavia, Italy.
Clinical Epidemiology and Biometry Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Eur J Drug Metab Pharmacokinet. 2021 Jan;46(1):155-159. doi: 10.1007/s13318-020-00660-2.
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] 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.
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.
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.
We can conclude that the HPLC-MS/MS assay represents a very good alternative to the reference.
白消安（Bu）是一种老药，但在造血干细胞移植前的预处理治疗中，仍被强烈推荐作为烷化剂。尽管其剂量给药是标准化的，且基于患者体重，但为了将其暴露量[浓度-时间曲线下面积（AUC）0 到无穷大 AUC]维持在狭窄的治疗范围内，需要进行治疗药物监测，如有必要，以尽可能短的时间调整剂量。本研究的目的是评估一种金标准分析方法和一种更快、更简便的新方法之间的一致性（根据 AUC 计算）。
我们分析了 37 名儿童（0.25-16 岁；4-62.5kg）和 11 名成人（21-59 岁；45-80kg）的 221 个血浆样本，共 52 个 AUC 值（ng h/mL）。同时，通过两种经过验证的分析方法计算药物暴露量。参考方法是一种结合紫外检测器（UV）的高效液相色谱（HPLC）检测法。测试方法采用三重四极杆质谱（MS）作为检测器；样品的净化程序不同且更快。
根据林氏一致性相关系数（CCC），以 Bu 暴露差异评估两种方法（参考方法和测试方法）之间的一致性，并通过 Bland-Altman 图表示。两种方法的 AUC 之间的 CCC 非常好（0.868；95%置信区间：0.802-0.935）。测量的精密度（用 Pearson 斜体“r”表示）为 0.872，准确性（用偏差校正因子计算）为 0.996。
我们可以得出结论，HPLC-MS/MS 测定法是一种非常好的替代参考方法的方法。
