含量测定类方法可靠性评价研究—理化Ⅰ类测定方法验证的统计指标和评价标准探讨

探索对药品主成分测定类方法可靠性评价的指标和标准。以美国药典论坛中<1200>、<1210>和USP通则<1225>指导原则为基础，以《中华人民共和国药典》2015年版二部赖诺普利含量测定项下方法为研究对象，应用统计学方法对含量测定方法进行了联合准确度和精密度、线性及范围的考察。该方法从统计学的角度，通过兼顾准确度、精密度和线性的实验设计，确保了该测定法所得到的结果具有较高的概率以达到标准中所规定的限度。该研究符合分析目标特征（analytical target profile，ATP）和决策准则（decision rules，DR）的理念，并与风险控制和科学公正检验的理念相一致。

In this paper,the exploring of the parameters and criteria for reliability evaluation of the API assays was conducted. An assay procedure according to the Monograph of Lisinoprolol described in ChP 2015 was established and the result was evaluated based on the approaches of<1200>,<1210>published in Pharmacopeia Forum of USP and<1225>documented in USP General Chapter. Method performance characteristics including combined precision-accuracy,linearity and range were investigated applying statistical method like least squared regression,hypothesis test,confidence interval,ensuring that the result meets the criteria described in the specification with a relatively high probability. The study was conducted in consistence with the concepts of analytical target profile(ATP)and decision rules(DR),as well as the scientific and justified practice.

[1] FDA. Guidance for Industry-Process Validation:General Principles and Practices[S]. 2011
[2] ICH Secretariat. ICH Harmonized Tripartite Guideline:Pharmaceutical Development Q8(R2)[S]. 2009
[3] ICH Secretariat. ICH Harmonized Tripartite Guideline:Quality Risk Management Q9[S]. 2005
[4] ICH Secretariat. ICH Harmonized Tripartite Guideline:Pharmaceutical Quality System Q10[S]. 2008
[5] MARTIN GP,KIMBER LB,CHRISTOPHER B,et al. Stimuli to the revision process:lifecycle management of analytical procedures:method development,procedure performance qualification,and procedure performance verification[J/OL]. Pharmacopeial Forum,39(5)[2017-10-15]. http://www.usp.org/uspnf/notices/stimuli-article-lifecyclemanagement-analyticalproceduresposted-comment
[6] USP 40-NF 35 General Chapter<1225>Validation of Compendial Procedure[S]. 2017:1780
[7] USP in Process Revision<1200>. Requirements for Compendial Validation[J/OL]. Pharmacopeial Forum,2013,39(6)[2017-10-15]. http://www.usppf.com/pf/pub/index.html
[8] USP in Process Revision<1210>. Statistical Tools for Procedure Validation[J/OL]. Pharmacopeial Forum,2014,40(5)[2017-10-15]. http://www.usppf.com/pf/pub/index.html.
[9] 中华人民共和国药典2015年版. 二部[S]. 2015:1457 ChP 2015. Vol Ⅱ[S]. 2015:1457
[10] CHOW SC. Statistical Design and Analysis in Pharmaceutical Science:Validation,Process Controls,and Stability[M]. New York:Marcel Dekker,Inc.,2002:31