NIDRS法结合GC-MS法分析吡罗昔康原料晶型及PⅡ晶型吡罗昔康片中1,2-二氯乙烷残留

目的：建立近红外（NIR）模型识别吡罗昔康原料药及片剂中原料药的晶型，结合PⅡ晶型原料药中1，2-二氯乙烷残留量超标，建立GC-MS法快速分析PⅡ晶型原料药生产的吡罗昔康片中1，2-二氯乙烷残留。方法：利用近红外光谱仪在12 000~4 000 cm^-1范围内采集吡罗昔康原料药及片剂的近红外光谱。分别针对吡罗昔康原料药建立NIR聚类分析模型，对片剂进行二阶导数化预处理，平滑点数21个，r阈值设置为97%，建立相关系数模型识别晶型差异；通过粉末X射线衍射法（PXRD法）验证原料药晶型识别结果。建立GC-MS方法测定吡罗昔康原料药中1，2-二氯乙烷残留；针对NIR相关系数模型筛选出吡罗昔康片PⅡ晶型的样品，测定其1，2-二氯乙烷残留。结果：PXRD和NIR聚类分析结果一致，吡罗昔康原料药为PⅠ、PⅡ 2种晶型；NIR模型判断吡罗昔康片中14批样品为PⅡ晶型，模型r阈值≥97%，剩余124批样品的r阈值<97%，为PⅠ晶型。GC-MS方法r为0.999 7，原料药和片剂的回收率分别为91.5%和90.9%，检出限为0.000 088%。GC-MS结果中，PⅡ类原料药二氯乙烷含量为0.036 6%，超出标准限度，PⅠ类未检出；NIR模型筛选出的PⅡ类吡罗昔康片中二氯乙烷含量均超出限度，PⅠ类片未检出。结论：本方法通过对原料药晶型的识别进而分析PⅡ晶型吡罗昔康片中1，2-二氯乙烷残留，方法简便快速，结果准确可靠。

Objective: Based on the overdose of 1, 2-dichloride ethane in the PⅡ crystalline form of piroxicam, NIR models were established to find out the PⅡ crystalline form of the raw materials in piroxicam and piroxicam tablets. According to the results of NIR models, GC-MS method was developed to analyze the 1, 2-dichloride ethane residue in piroxicam tablets.Methods: In the wavelength range of 12000-4000 cm^-1, NIR spectrometer was used to collect spectrums. For distinguishing the crystalline forms, NIR cluster analysis model was set up for piroxicam raw materials and correlation coefficient model for tablets, in which ther level was set to 97% and the amount of smooth points was 21 with the second derivative pretreatment of spectrums. PXRD method was used to validate the analysis results from NIR cluster analysis model. GC-MS method was developed to analyze the 1, 2-dichloride ethane residue in piroxicam and tablets made of the PⅡ crystalline form material based on the analysis results of NIR models.Results: The PXRD and NIR cluster analysis model results were consistent, and piroxicam material and tablets were all divided into two crystalline forms by NIR models. All 14 batches of tablets were of PⅡ type with r≥97%, and 124 batches of tablets were of PⅠ type with r<97%. The recoveries of piroxicam raw material and tablets were 91.5% and 90.9%, with good linear relationship (r=0.9997). The detection limit for tablets was 0.000088%. For raw material, the concentration of 1, 2-dichloride ethane in PⅡ type was 0.0366% and zero in PⅠ type as determined by GS-MS. For tablets, the concentrations of 1, 2-dichloride ethane in PⅡ type were beyond the standard limitation and were zero in PⅠ type.Conclusion: The method is convenient, quick and accurate in determination of the crystallineform difference and the 1, 2-dichloride ethane residue in the PⅡ crystalline form of piroxicam tablets.

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