Development and Validation of the New Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Unbound Tacrolimus in the Plasma Ultrafiltrate of Transplant Recipients
(1) Background: Only unbound tacrolimus particles are considered to be active and capable of crossing cellular membranes. Thus, the free-drug concentration might be better associated with clinical effects than the total drug concentration used for dosage adjustment. We propose a new, fully validated...
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| Main Authors: | , , , , , , |
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| Format: | Book |
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MDPI AG,
2022-03-01T00:00:00Z.
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| Summary: | (1) Background: Only unbound tacrolimus particles are considered to be active and capable of crossing cellular membranes. Thus, the free-drug concentration might be better associated with clinical effects than the total drug concentration used for dosage adjustment. We propose a new, fully validated online liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for unbound tacrolimus concentration measurement. (2) Methods: The determination of the unbound tacrolimus concentration in plasma ultrafiltrate was performed with the Nexera LC system with LCMS-8050 triple quadrupole MS using ascomycin as an internal standard. Chromatographic separation was made using a HypurityC18 analytical column. MS/MS with electrospray ionization and positive-ion multiple-reaction monitoring was used. The unbound tacrolimus level was determined in 36 patients after solid organ transplantation (<i>n</i> = 140). (3) Results: A lower limit of quantification 0.1 pg/mL was achieved, and the assay was linear between 0.1 and 20 pg/mL (R<sup>2</sup> = 0.991). No carry-over was detected. The within-run and between-run accuracies ranged between 97.8-109.7% and 98.3-107.1%, while the greatest imprecision was 10.6% and 10.7%, respectively. Free tacrolimus in patients' plasma ultrafiltrate varied between 0.06 and 18.25 pg/mL (median: 0.98 pg/mL). (4) Conclusions: The proposed method can be easily implemented. The significance of the unbound tacrolimus concentration needs to be investigated. This may facilitate the individualization and optimization of immunosuppressive treatment. |
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| Item Description: | 10.3390/pharmaceutics14030632 1999-4923 |