Linnet Kristian
Laboratory of Clinical Biochemistry, Psychiatric University Hospital, Risskov, Denmark.
Clin Chem Lab Med. 2005;43(4):394-9. doi: 10.1515/CCLM.2005.071.
A recently proposed procedure for estimating the limit of detection (LoD) of an assay using a partly non-parametric approach is applied to five HPLC drug assays. The non-parametrically determined 95th percentile of the blank measurements (LoB) is obtained as the value of the N (95/100) + 0.5 ordered observations. The LoD is the lowest level of analyte that is likely to yield a measured result exceeding the LoB. The LoD equals LoB + c(beta) x SD(S), where SD S is the analytical SD at low concentrations, and c(beta) = z(1-beta)/(1-1/(4 x f )) (f = degrees of freedom). c(beta) approximately 1.65 for a type II error of 5%. The blank distributions deviated significantly from normality for four of the five assays because of skewness to the right. The estimated LoB ranged from 3.3 to 10.2 nmol/L. The LoDs were in the interval from 7.8 to 17.2 nmol/L. A new procedure for estimation of the standard error (SE) of the estimated LoD that is partly based on the bootstrap principle showed good performance in simulation studies. In conclusion, the partly non-parametric procedure for estimation of the LoD of typical HPLC drug assays was found to be a suitable approach.
一种最近提出的使用部分非参数方法估计分析方法检测限（LoD）的程序被应用于五种高效液相色谱（HPLC）药物分析。通过对N（95/100）+ 0.5个有序观测值求值，得到非参数确定的空白测量值的第95百分位数（LoB）。LoD是可能产生超过LoB测量结果的最低分析物水平。LoD等于LoB + c(β)×SD(S)，其中SD(S)是低浓度下的分析标准差，且c(β) = z(1-β)/(1 - 1/(4×f))（f =自由度）。对于5%的II类错误，c(β)约为1.65。由于五个分析中有四个的空白分布向右偏斜，显著偏离正态性。估计的LoB范围为3.3至10.2 nmol/L。LoD在7.8至17.2 nmol/L的区间内。一种部分基于自助法原理估计估计LoD标准误差（SE）的新程序在模拟研究中表现良好。总之，发现用于估计典型HPLC药物分析LoD的部分非参数程序是一种合适的方法。
