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求助英文文献全文:https://pubmed.ncbi.nlm.nih.gov/38193880/

药师 · 最后编辑于 2024-11-05 · IP 浙江浙江
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Ther Drug Monit




. 2024 Feb 1;46(1):49-56. doi: 10.1097/FTD.0000000000001135. Epub 2023 Sep 26.

Determining Plasma Tacrolimus Concentrations Using High-Performance LC-MS/MS in Renal Transplant Recipients

Mirabel Alonge 1 2Janet K Coller 2Stephanie E Reuter 3Shilpanjali Jesudason 4Benedetta C Sallustio 2

Affiliations Expand

Abstract

Background: Whole-blood therapeutic drug monitoring of tacrolimus is conducted to maintain tacrolimus concentrations within a safe and effective range. Changes in hematocrit cause variability in blood concentrations of tacrolimus because it is highly bound to erythrocytes. Measuring plasma concentrations may eliminate this variability; however, current methods have limitations owing to the use of cross-reactive immunoassays, plasma separation at nonbiological temperatures, and lack of clinical validation. This study aimed to develop and validate a clinically applicable method to measure plasma tacrolimus concentrations in renal transplant recipients and to examine the concentration differences between genotypic CYP3A5 expressors and nonexpressors.

Methods: Plasma tacrolimus concentrations were measured in 9 stable renal transplant recipients who were genotypic CYP3A5 expressors or nonexpressors. Tacrolimus was extracted from plasma using solid-phase extraction, and liquid chromatography-tandem mass spectrometry was used for detection and quantitation.

Results: This assay was sensitive, selective, and linear between 100 and 5000 ng/L, with intraassay and interassay imprecision and inaccuracy <10% and <5% respectively. The extraction recovery of tacrolimus and ascomycin was 74%. Matrix ion suppression effects were 31.5% and 35% with overall recovery of 50.6% and 48.3% for tacrolimus and ascomycin, respectively. Whole-blood concentrations accounted for approximately 46% of the variation in plasma concentrations in CYP3A5 expressors and nonexpressors. No difference in dose-adjusted whole-blood and plasma concentrations was observed between CYP3A5 expressors and nonexpressors.

Conclusions: This assay is clinically applicable with excellent performance and demonstrated that tacrolimus plasma concentrations highly correlated with whole-blood concentrations.

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