Comparing the effect of isotopically labeled or structural analog internal standards on the performance of a LC-MS/MS method to determine ciclosporin A, everolimus, sirolimus and tacrolimus in whole blood

Clinical Chemistry and Laboratory Medicine : CCLM
Henar ValbuenaEberhard Wieland

Abstract

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is routinely used for analysis of immunosuppressive drugs. This study investigated whether replacing analog internal standards (ANISs) with isotopically labeled internal standards (ILISs) has an impact on the performance of a LC-MS/MS method for the quantification of tacrolimus (TAC), sirolimus (SIR), ciclosporin A (CsA) and everolimus (EVE) in whole blood. Following hemolysis, protein precipitation, and extraction with either ANISs (ascomycin, desmethoxy-rapamycin, CsD), or ILISs (TAC-13C,D2; SIR-13C,D3; CsA-D12; EVE-D4), samples were centrifuged and injected into a LC-MS/MS device equipped with a C18 reversed phase column. The effect of the two ISs on the linearity, precision, accuracy, trueness, matrix effects, and carryover was investigated by using the same patient-, proficiency testing-, and quality control samples. Statistical analysis of agreement between results includes a standard random effects model and Passing-Bablok regression. Within-day imprecision was <10%, between-day <8%, and trueness 91%-110% for all the analytes with both ISs. No carryover or matrix effects were observed. The median accuracy was -2.1% for CsA, 9.1% for EVE, 12.2% for SIR, and -1.2% f...Continue Reading

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Citations

May 1, 2019·Annals of Laboratory Medicine·Hyojin ChaeUNKNOWN Clinical Mass Spectrometry Research Committee of Korean Society of Clinical Chemistry
Dec 12, 2020·Annals of Laboratory Medicine·Hyun-Ki KimUNKNOWN Clinical Mass Spectrometry Research Committee of the Korean Society of Clinical Chemistry

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