Affinity Column Mediated Immunometric Assay를 이용한 혈중 Tacrolimus 농도 검사법의 평가
Performance Evaluation of Affinity Column Mediated Immunometric Assay for Tacrolimus
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배경 : Tacrolimus는 적정 치료농도범위가 좁고 약물용량과 혈중농도의 상관 관계가 낮아 혈중약물농도 측정을 통한 감시가 필수적이다. 전처리 과정이 필요없는 Affinity Column Mediated Immunometric Assay (ACMIA)를 이용한 Dimension RxL Max (Dade Behring)의 tacrolimus 혈중농도측정에 대 한 수행능을 평가하고자 하였다. 방법 : Clinical and Laboratory Standards Institute 지침 에 준하여 ACMIA를 이용한 tacrolimus 혈중농도측정에 대해 정밀도, 직선성, 검출한계를 분석하고, 빌리루빈과 chyle 및 적 혈구용적율에 대한 간섭현상을 평가하였다. 또한 microparticle enzyme immunoassay (MEIA) (IMx Tacrolimus II, Abbott Laboratories)와 liquid chromatography-tandem mass spectrometry (LC-MS/MS) (Waters 2795 Quattromicro API, Micromass)의 tacrolimus 측정 결과와 ACMIA에 의한 측정 결과와의 상관관계를 분석하였다. 결과 : 저∙중∙고농도의 총 변이계수는 각각 12.8%, 9.0%, 6.7%였고, tacrolimus 농도 3.1 ng/mL부터 35.4 ng/mL에서 직선성을 보였다. 최소농도 검출 한계는 0.24 ng/mL, 기능적 민감도는 0.72 ng/mL이었으며, 빌리루빈과 chyle에 대해 간섭효과를 나타나지 않았고, 적혈구용적률 변화에 따른 tacrolimus 검사값의 영향은 미미하였다. ACMIA에 의한 tacrolimus 측정치는 MEIA와는 0.950, LC-MS/MS에 대해서는 0.946 의 상관계수를 나타내었다. 결론 : ACMIA에 의한 tacrolimus 측정은 정밀도, 직선성, 측정한계, 다른 물질에 의한 간섭 및 MEIA와 LC-MS/MS에 대한 상관성 항목에 대해 만족스러운 검사 수행능을 보였다. 따 라서 기존 검사법보다 빠른 시간 안에 신빙성 있는 검사결과의 보고가 가능하여 이식 환자의 진료에 도움을 줄 수 있으리라 예 상된다.
Abstract
Background : Therapeutic drug monitoring (TDM) of tacrolimus is essential because of narrow therapeutic range and poor correlation of dose to blood concentration. Affinity Column Mediated Immunometric Assay (ACMIA) does not require a pretreatment steps in measurement of tacrolimus. In this study, we evaluated the performance of tacrolimus assay using ACMIA (Dimension RxL Max, Dade Behring). Methods : The imprecision, the linearity and the detection limits and the interferences by bilirubin and chyle, and correlation with hematocrit for tacrolimus by ACMIA were evaluated according to Clinical and Laboratory Standards Institute guidelines EP5-A2, EP6-A, EP17-A, EP9-A2, and EP7- A2. Method comparison studies with microparticle enzyme immunoassay (MEIA) (IMx Tacrolimus II, Abbott Laboratories) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) (Waters 2795 Quattromicro API, Micromass) were also performed. Results : The total imprecision for low, middle and high level was 12.8%, 9.0% and 6.7%, respectively. The range of tacrolimus from 3.1 ng/mL to 35.4 ng/mL showed a clinically relevant linearity. The limit of detection and the functional sensitivity were 0.24 ng/mL and 0.72 ng/mL, respectively. Tacrolimus concentration measurement (Tac-CM) with ACMIA did not show significant interferences with bile and chyle and also did not show significant correlation with hematocrit. In comparison study for Tac-CM with MEIA and LC-MS/MS, Tac-CM with ACMIA showed a good correlation with MEIA (r=0.950) and LC-MS/MS (r=0.946). Conclusions : The imprecision, linearity, detection limits, interference and correlation of Tac-CM with ACMIA were suitable for clinical use. Tac-CM with ACMIA could reduce turn around time and help clinicians to manage transplant patients on immunosuppressant therapy.
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