在生物標(biāo)志物分析方法學(xué)驗證項中，穩(wěn)定性驗證是難點。與藥動學(xué)分析不同的是，生物標(biāo)志物分析待測物為內(nèi)源性物質(zhì)，其穩(wěn)定性與標(biāo)準(zhǔn)品（一般為重組蛋白）有很大不同。所以，生物標(biāo)志物穩(wěn)定性驗證樣品應(yīng)采用內(nèi)源性真實樣本。但是受分析方法變異影響，內(nèi)源性真實樣本的準(zhǔn)確濃度無法得知，而且難以獲取新鮮的未凍存過的樣本，最終導(dǎo)致穩(wěn)定性的接受標(biāo)準(zhǔn)難以界定。運用趨勢控制圖和計算機分析等手段可以更準(zhǔn)確地判斷生物標(biāo)志物的穩(wěn)定性。

In biomarker bioanalytical method validation, one of the most challenges is stability. Compared with pharmacokinetic (PK) assays, the analytes of biomarker assay is endogenous. The stability of endogenous analytes is differed with its corresponding recombinant reference standard. To that end, biomarker stability evaluation should be performed using endogenous incurred sample. However, the accurate concentration of endogenous sample is difficult to assess due to the assay variation. In addition, it is hard to acquire fresh unfrozen sample. All above factors lead to the difficulty of defining acceptance criteria for stability evaluation. Trending chart and computational analysis could be used to determine biomarker stability more accurately.

R967

“十三五”重大專項（2018ZX09201017-008）