技术共探丨8大解读，带你摸清FDA/EMA/NMPA生物分析指导原则套路

这些数据可被用于支持药品的安全性和有效性，或根据毒动学、药动学和生物等效性试验的结果做出关键性决定（包括非临床和临床）；

To support safety and efficacy based on PK and TK parameter determinations;

Human clinical pharmacology, BA and BE requiring PK evaluations;

Non-clinical studies;

Biological matrices, such as blood, plasma, serum, urine, tissue;

应该使用至少6个来源的适宜的空白基质来证明选择性，它们被分别分析并评价干扰；

Use of fewer sources is acceptable in case of rare matrices；

Alternatively, back-conversion of a metabolite can be checked by applying incurred sample reanalysis. However, in this case potential back conversion during sample processing cannot be ruled out.

hemolyzed samples, lipemic samples or samples from special populations can be included in the selectivity assessment depending on the intended use.

分为批内准确度和精密度、批间准确度和精密度；

Accuracy and Precision（ A & P ） should be established with at least three independent A & P runs, four QC levels per run (LLOQ, L, M, H QC), and ≥five replicates per QC level.

Extracted samples at L, M and H QC concentrations versus extracts of blanks spiked with the analyte post extraction (at L, M and H)；

涉及stock solution  stability及working solution stability；

对于同位素内标，在确定无isotope exchange时，可不考察其稳定性；

从冰箱储存条件到室温或样品处理温度，基质中分析物的冷冻和融化稳定性；

基质中分析物在冰箱储存的长期稳定性；

处理过的样品在室温下或在试验过程储存条件下的稳定性；

仅涉及stock solution stability，未提及working solution stability；

对于同位素内标是否考察其稳定性未做说明；

Stock solutions should not be made from reference materials that are about to expire unless the purity of the analyte in the stock solutions is reestablished.

毒动学试验，每个物种一次；

所有关键性的生物等效性试验；

首次用于人体的药物试验；

首次用于患者的药物试验；