University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Hanzeplein 1, 9700 RB Groningen, the Netherlands; University of Groningen, Department of Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, the Netherlands.
J Chromatogr A. 2023 Aug 2;1702:464086. doi: 10.1016/j.chroma.2023.464086. Epub 2023 May 20.
Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is the golden standard for immunosuppressants analyses, where optimising throughput by parallel chromatography can reduce costs and turnaround time. We aimed to double our system throughput using a dual LC-MS/MS setup. Therefore, two independent UPLC systems were hyphenated to one triple quadrupole MS, with staggered injections from one autosampler on alternating columns. The method simultaneously measured the analytes tacrolimus, sirolimus, everolimus, and cyclosporin A in whole blood using isotope dilution, with a run time of 1.5 min. Using the dual LC-MS/MS system, net run-to-run time improved from 2.3 to 0.98 min per injection, where throughput increased from 26 to 61 injections per hour. For Performance Qualification, 1101 clinical samples were measured on the dual LC-MS/MS system in addition to the standard system, during a period of one month, and the results were compared using Passing Bablok regression and Bland Altman analysis. There was excellent agreement for all four analytes, with regression slopes of 0.98-1.02x and intercepts of -0.11-0.88 µg/L. Minor bias was demonstrated between the systems with mean differences from -0.93 to 1.43%. In conclusion, the throughput was doubled and idle MS time was reduced with good agreement to the standard system. Currently, the method is applied for clinical routine with frequent peak intensities of >180 injections per day.
液相色谱-串联质谱法（LC-MS/MS）是免疫抑制剂分析的金标准，通过并行色谱优化通量可以降低成本和周转时间。我们旨在使用双 LC-MS/MS 系统将系统通量提高一倍。因此，将两个独立的 UPLC 系统与一个三重四极杆质谱仪串联，使用交替柱从一个自动进样器交错进样。该方法使用同位素稀释法同时测量全血中的分析物他克莫司、西罗莫司、依维莫司和环孢素 A，运行时间为 1.5 分钟。使用双 LC-MS/MS 系统，每个进样的净运行时间从 2.3 分钟提高到 0.98 分钟，通量从每小时 26 个增加到 61 个。在性能验证期间，除了标准系统外，还在一个月的时间内在双 LC-MS/MS 系统上测量了 1101 个临床样本，并使用 Passing Bablok 回归和 Bland Altman 分析比较结果。所有四种分析物的结果都非常一致，回归斜率为 0.98-1.02x，截距为-0.11-0.88μg/L。两个系统之间存在较小的偏差，平均差异为-0.93 至 1.43%。总之，通量提高了一倍，闲置 MS 时间减少，与标准系统具有良好的一致性。目前，该方法已应用于临床常规，每天的峰强度>180 次。
