本文選題：甲磺酸伊馬替尼 + 甲基哌嗪��； 參考：《浙江工業(yè)大學(xué)》2017年碩士論文

【摘要】：甲基哌嗪和肼在合成抗癌藥物甲磺酸伊馬替尼(MIM)過程中,均屬于關(guān)鍵物料,物料的引入、遷移、去除,需要闡述清楚。建立高靈敏度的測定方法對于工藝研究、雜質(zhì)控制、質(zhì)量標(biāo)準(zhǔn)制訂等具有十分重要的意義。固相萃取(SPE)預(yù)處理伊馬酸(MIM60)后用氣相色譜色譜法(GC)測定甲基哌嗪的含量,苯甲醛衍生肼后用高效液相色譜(HPLC)測定甲磺酸伊馬替尼及其中間體伊馬胺(MIM50)中肼的含量,使兩個色譜測定分析方法的靈敏度、準(zhǔn)確度和精密度進(jìn)一步提高。結(jié)果表明,固相萃取氣相色譜法測定伊馬酸中甲基哌嗪的含量,其溶液在24小時內(nèi)穩(wěn)定,濃度范圍在2.49-17.57μg/mL的線性相關(guān)系數(shù)(r)為1.0000,定量限(QL)為2.49μg/mL,檢測限(DL)為0.83μg/mL,濃度在2.50-15.00μg/mL時回收率接近100%,方法精密度考察的相對標(biāo)準(zhǔn)偏差(RSD)為1.3%。分析方法準(zhǔn)確穩(wěn)定可靠,可以有效定量伊馬酸中甲基哌嗪的含量,已有批次樣品小于檢測限。苯甲醛衍生化高效液相色譜法測定伊馬胺和甲磺酸伊馬替尼中肼的含量,其溶液在24小時內(nèi)穩(wěn)定,在甲磺酸伊馬替尼測定中,濃度范圍在0.023-0.180μg/mL的線性相關(guān)系數(shù)為0.9995,伊馬胺測定中,濃度范圍在2.25-18.00μg/mL的線性相關(guān)系數(shù)為1.0000,定量限為0.023μg/mL,檢測限為0.008μg/mL,甲磺酸伊馬替尼測定肼的濃度為0.023-0.128μg/mL時回收率接近100%,伊馬胺測定肼的濃度為2.25-12.75μg/mL時回收率接近100%,甲磺酸伊馬替尼測定肼的方法精密度考察的相對標(biāo)準(zhǔn)偏差為1.5%,伊馬胺測定肼的方法精密度的相對標(biāo)準(zhǔn)偏差為0.26%。分析方法準(zhǔn)確穩(wěn)定可靠,可以有效定量伊馬胺和甲磺酸伊馬替尼中肼的含量,伊馬胺已有批次樣品最大為0.02%,甲磺酸伊馬替尼已有批次小于檢測限。
[Abstract]:Both methylpiperazine and hydrazine are the key materials in the process of synthesizing the anticancer drug imatinib mesylate. The introduction, migration and removal of the materials need to be explained clearly. It is very important to establish a high sensitivity method for process research, impurity control and quality standard formulation. The content of methylpiperazine was determined by gas chromatography (GC), and the content of hydrazine in imatinib mesylate and its intermediate imatinib (MIM50) was determined by high performance liquid chromatography (HPLC) after benzaldehyde derivatization of hydrazine. The sensitivity, accuracy and precision of the two chromatographic methods were further improved. The results showed that the content of methylpiperazine in imaric acid was determined by solid phase extraction gas chromatography, and the solution was stable within 24 hours. The linear correlation coefficient (r) of 2.49-17.57 渭 g / mL was 1.00, the quantitative limit was 2.49 渭 g / mL, the detection limit was 0.83 渭 g / mL, and the recovery was close to 100 when the concentration was 2.50-15.00 渭 g / mL. The relative standard deviation (RSDs) of the method was 1.3B. The method is accurate, stable and reliable, and can be used to determine the content of methylpiperazine in imaric acid. The content of hydrazine in imamide and imatinib mesylate was determined by high performance liquid chromatography with benzaldehyde derivatization. The solution of hydrazine was stable within 24 hours. The linear correlation coefficient was 0.9995 in the range of 0.023 ~ 0.180 渭 g / mL for imatinib mesylate, and the linear correlation coefficient was 0.9995 for the determination of imatinib mesylate in the range of 0.023 ~ 0.180 渭 g / mL. In the range of 2.25-18.00 渭 g / mL, the linear correlation coefficient is 1.00000.The limit of determination is 0.023 渭 g / mL, the detection limit is 0.008 渭 g / mL, the recovery of imatinib mesylate is 0.023-0.128 渭 g / mL, the concentration of hydrazine is 2.25-12.75 渭 g / mL, the recovery of imadine is close to 100g / mL, and the limit of detection is 0.008 渭 g / mL. The relative standard deviation of the method for the determination of hydrazine by tinnitine was 1.5 and the RSD of the method for the determination of hydrazine was 0.26. The method is accurate, stable and reliable, and can be used to determine the content of hydrazine in imatinib and imatinib mesylate effectively. The maximum value of imatinib in the batch is 0.02g, and the batch of imatinib mesylate is less than the detection limit.
【學(xué)位授予單位】：浙江工業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：TQ460.72;O657.7

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