近红外光谱法测定尼莫地平片剂尼莫地平含量的4个分析模型所给出的预测值的准确性的比较

用仪器所附的积分球分析模块采集了尼莫地平片剂的片状和将片剂粉碎后的粉末样品的漫反射近红外光谱图。另用所附片剂分析模块采集了尼莫地平片剂的反射和透射近红外光谱图。分别将上述4种近红外光谱(NIRS)图用TQ Analyst 9.0软件建立了4个定量分析的模型(模型1,2,3,4)。另从3个批次各取5个样品,用《中华人民共和国药典(2015版)》中的高效液相色谱法(HPLC)测定其中尼莫地平的含量作为对上述4种模型的预测值的外部验证。根据内部验证和交叉验证所得到的4种模型的各项参数及其性能指数,可见模型2为其中的最优模型。将上述15个样品的NIRS图分别引入4种模型,获得其中尼莫地平含量的预测值;经与HPLC测定值比较,可知4种模型的预测值与HPLC测定值之间的相对误差依次为-2.41%~2.68%,-0.81%~1.18%,-5.03%~4.55%和-5.99%~5.56%。其中以模型2的相对误差最小,模型1稍大,模型3和4最大,但较接近。根据t检验法(α=0.05)的结果,4种模型所得的预测值与HPLC测定值之间无显著差异,因而4种模型均可用于尼莫地平的检测。模型2预测值的相对误差较小,但测定时需要样品前处理,使整个分析时间延长,可考虑应用于均匀性较差或形状有差异的样品的测定。其余3个模型预测值的相对误差较大,但不需要对片剂进行前处理,分析时间较短,可根据不同需要选择应用这4种模型。特别是用模型3和模型4可同时获得样品的反射和透射近红外光谱定量的信息,可对测定结果进行对照试验。

Comparative Accuracy of Prediction Values of Contents of Nimodipine Given by the 4 Analytical Models for Near Infrared Spectrometric Analysis of Nimodipine Tablets

Diffuse reflection near infrared spectra(NIRS)of the nimodipine(NMDP)tablets and of its powder obtained by crushing and grinding of the tablets were collected by the integral sphere-analytical module annexed to the NIR spectrometer.Furthermore,reflection NIRS and transmission NIRS of the NMDP tablet were collected by the annexed analytical module for tablet.And then 4quantitative analytical models(named model 1,2,3and 4)were derived separately from the 4NIRS using TQ Analyst 9.0software.On the other hand,Fifteen samples of the NMDP tablet were collected by taking 5samples from each of 3batches of the drug,and analyzed for their NMDP contents by the method of HPLC given in the“Pharmacopoeia of PRC(2015)”.The data obtained were used for external veritication of the prediction values of NMDP in the samples given by the 4models.As shown by the statistical parameters and the performance indexes found by the internal and cross-verification,the model 2was found to be best among the 4models.By introducing the NIRS of the 15samples into the 4models separately,and data of prediction contents of NMDP in these samples were obtained.By comparing with the values of NMDP contents found by HPLC,the relative errors found between the prediction values given by the 4models and the HPLC data were given in the following ranges:-2.41%to 2.68%(for model 1),0.81%to 1.18%(for model 2),-5.03%to 4.55%(for model 3)and-5.99%to 5.56%(for model 4).It was obvious that the relative errors of model 2were the smallest,and of model 1were larger,and of model 3and 4were the largest,but quite close to each other.However,no significant differences were found between the results of HPLC analysis and prediction values given by any of the 4models according to the results of t-test(α=0.05).Hence,any one of the 4models could be applied to the determination of NMDP in the drug tablet.Model 2gave prediction values with smaller relative error,but sample pretreatment was required in this case and longer time was required for the whole analytical process,model 1could be considered to apply to the determination of NMDP in the drug tablet with poor uniformity or various shapes.Although the other 3 models gave prediction values with relatively larger relative errors,but they gave more rapid analysis since no sample pretreatment was required.Especially,model 3and 4 could give reflection and transmission NIRS informations simultaneously and were favourable for comparative study.