CN101487827A - Indirect test method for Miglitol purity - Google Patents
Indirect test method for Miglitol purity Download PDFInfo
- Publication number
- CN101487827A CN101487827A CNA2009100961915A CN200910096191A CN101487827A CN 101487827 A CN101487827 A CN 101487827A CN A2009100961915 A CNA2009100961915 A CN A2009100961915A CN 200910096191 A CN200910096191 A CN 200910096191A CN 101487827 A CN101487827 A CN 101487827A
- Authority
- CN
- China
- Prior art keywords
- miglitol
- purity
- test method
- piperidine
- acetoxymethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 title claims abstract description 81
- 229960001110 miglitol Drugs 0.000 title claims abstract description 81
- 238000010998 test method Methods 0.000 title claims abstract description 26
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims abstract description 39
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 32
- 238000005886 esterification reaction Methods 0.000 claims abstract description 26
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 16
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000006640 acetylation reaction Methods 0.000 claims abstract description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 6
- 238000010606 normalization Methods 0.000 claims abstract description 6
- 239000000758 substrate Substances 0.000 claims abstract description 6
- 230000014759 maintenance of location Effects 0.000 claims abstract description 5
- 230000021736 acetylation Effects 0.000 claims abstract description 3
- 238000005917 acylation reaction Methods 0.000 claims abstract description 3
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 3
- 238000004587 chromatography analysis Methods 0.000 claims abstract description 3
- 238000004817 gas chromatography Methods 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 230000035484 reaction time Effects 0.000 claims description 10
- 239000003054 catalyst Substances 0.000 claims description 6
- 238000004458 analytical method Methods 0.000 claims description 2
- 238000012360 testing method Methods 0.000 abstract description 7
- 239000012295 chemical reaction liquid Substances 0.000 abstract description 3
- 150000002148 esters Chemical class 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 239000007789 gas Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000001514 detection method Methods 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- -1 sorbitol ester Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
Images
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
本发明公开了一种米格列醇纯度的间接测试法，包括以下步骤：1)以待测的米格列醇作为底物，醋酐作为乙酰化试剂进行乙酰化反应，得含有乙酸－β－(3，4，5－三乙酰氧基－2－乙酰氧甲基－1－哌啶)－乙酯的酯化反应液；或者以待测的米格列醇作为底物，丙酸酐作为酰化试剂，在无水吡啶的催化作用下进行酰化反应，得含有丙酸－β－(3，4，5－三乙酰氧基－2－乙酰氧甲基－1－哌啶)－乙酯的酯化反应液；2)对上述酯化反应液进行气相色谱分析，得到其各组分在气相色谱中的保留时间以及峰面积，除去轻组分的峰面积后，根据归一化法推算获得米格列醇的纯度。本发明的间接测试法具有测试方法简单、测试结果准确的特点。
The invention discloses an indirect test method for the purity of miglitol, which comprises the following steps: 1) using miglitol to be tested as a substrate and acetic anhydride as an acetylation reagent to carry out acetylation reaction to obtain acetic acid-β -(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester esterification reaction solution; or use miglitol to be tested as a substrate and propionic anhydride as a Acylating reagent, carry out acylation reaction under the catalysis of anhydrous pyridine, and obtain propionic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl The esterification reaction liquid of ester; 2) carry out gas chromatographic analysis to above-mentioned esterification reaction liquid, obtain the retention time and peak area of its each component in gas chromatogram, after removing the peak area of light component, according to normalization method Calculate the purity of miglitol obtained. The indirect test method of the invention has the characteristics of simple test method and accurate test result.
Description
技术领域 technical field
本发明涉及一种米格列醇纯度的间接测试法。The invention relates to an indirect test method for the purity of miglitol.
背景技术 Background technique
米格列醇是一种II型糖尿病抑制药物，其结构为(I)：Miglitol is a type II diabetes inhibitory drug, its structure is (I):
由于米格列醇为多羟基化合物，分子间作用力强(主要为氢键)，同时分子量较大，挥发度低，而且极性强，不能直接进行气相色谱(GC)检测。目前关于米格列醇的检测多用高效液相色谱法(HPLC)，其存在着以下不足之处：(1)米格列醇对检测器挑剔，因无紫外吸收，所以不能用灵敏度高的紫外检测器；(2)现在一般用视差折光检测器，却存在着灵敏度低、易受环境温度以及流动相影响的缺点，导致检测结果误差大；(3)该法对设备要求高，而且操作复杂。Since miglitol is a polyhydroxy compound with strong intermolecular forces (mainly hydrogen bonds), large molecular weight, low volatility, and strong polarity, it cannot be directly detected by gas chromatography (GC). At present, high-performance liquid chromatography (HPLC) is mostly used in the detection of miglitol, which has the following shortcomings: (1) Miglitol is picky about the detector, because it has no ultraviolet absorption, so it cannot be used with sensitive ultraviolet light. (2) Parallax refractive index detectors are generally used now, but they have the disadvantages of low sensitivity, being easily affected by ambient temperature and mobile phase, resulting in large errors in detection results; (3) This method requires high equipment and is complicated to operate .
与HPLC相比，GC具有检测速度快、灵敏度高以及操作简便、应用广泛的优点，因此如果能利用GC来间接获得米格列醇的纯度就非常有必要。Compared with HPLC, GC has the advantages of fast detection speed, high sensitivity, easy operation, and wide application. Therefore, it is very necessary to use GC to indirectly obtain the purity of miglitol.
发明内容 Contents of the invention
本发明要解决的技术问题是提供一种米格列醇纯度的间接测试法。The technical problem to be solved by the present invention is to provide an indirect test method for the purity of miglitol.
为了解决上述技术问题，本发明提供一种米格列醇纯度的间接测试法，包括以下步骤：In order to solve the problems of the technologies described above, the invention provides a kind of indirect test method of Miglitol purity, comprising the following steps:
1)、以待测的米格列醇作为底物，醋酐作为乙酰化试剂进行乙酰化反应，醋酐：米格列醇的质量比＝3～30：1，反应温度85～105℃，反应时间1～3h；得含有乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯的酯化反应液；1), use the miglitol to be tested as the substrate, and acetic anhydride as the acetylation reagent to carry out the acetylation reaction, the mass ratio of acetic anhydride:miglitol=3～30:1, the reaction temperature is 85～105°C, The reaction time is 1 to 3 hours; an esterification reaction solution containing acetic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester is obtained;
2)、对含乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯的酯化反应液进行气相色谱分析，得到其各组分在气相色谱中的保留时间以及峰面积，除去轻组分的峰面积后，根据归一化法推算获得米格列醇的纯度。2), carry out gas chromatographic analysis to the esterification reaction solution containing acetic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester, and obtain its components According to the retention time and peak area in gas chromatography, after removing the peak area of light components, the purity of miglitol was calculated according to the normalization method.
作为本发明的米格列醇纯度的间接测试法的改进，醋酐：米格列醇的质量比＝10～13：1，反应温度90～100℃，反应时间2h。As an improvement of the indirect test method for the purity of miglitol in the present invention, the mass ratio of acetic anhydride:miglitol=10-13:1, the reaction temperature is 90-100°C, and the reaction time is 2h.
作为本发明的米格列醇纯度的间接测试法的另一种改进，步骤1)采用无水吡啶作为催化剂，无水吡啶：米格列醇的质量比＝0.4～0.8：1，反应时间1～2.5h。As another improvement of the indirect test method of the purity of miglitol of the present invention, step 1) adopts anhydrous pyridine as a catalyst, anhydrous pyridine: the mass ratio of miglitol=0.4～0.8:1, and the reaction time is 1 ~2.5h.
作为本发明的米格列醇纯度的间接测试法的进一步改进，醋酐：米格列醇的质量比＝7～10：1，反应温度90～100℃，反应时间2h。As a further improvement of the indirect test method for the purity of miglitol in the present invention, the mass ratio of acetic anhydride:miglitol=7-10:1, the reaction temperature is 90-100°C, and the reaction time is 2h.
本发明还同时提供了另一种米格列醇纯度的间接测试法，包括以下步骤：The present invention also provides another indirect test method of Miglitol purity simultaneously, comprising the following steps:
1)、以待测的米格列醇作为底物，丙酸酐作为酰化试剂，在无水吡啶的催化作用下进行酰化反应，丙酸酐：米格列醇的质量比＝8～12：1，无水吡啶：米格列醇的质量比＝0.4～0.8：1，反应温度95～100℃，反应时间2～2.5h；得含有丙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯的酯化反应液；1), using the miglitol to be tested as the substrate, propionic anhydride as the acylating reagent, and carrying out the acylation reaction under the catalysis of anhydrous pyridine, the mass ratio of propionic anhydride:miglitol=8～12: 1. Mass ratio of anhydrous pyridine:miglitol=0.4～0.8:1, reaction temperature 95～100℃, reaction time 2～2.5h; The esterification reaction solution of oxy-2-acetoxymethyl-1-piperidine)-ethyl ester;
2)、对丙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯的酯化反应液进行气相色谱分析，得到其各组分在气相色谱中的保留时间以及峰面积，除去轻组分的峰面积后，根据归一化法推算获得米格列醇的纯度。2), carry out gas chromatography analysis to the esterification reaction solution of propionic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester, obtain its each group According to the retention time and peak area in gas chromatography, after removing the peak area of light components, the purity of miglitol was calculated according to the normalization method.
本发明方法的步骤1)，可如下式所示：Step 1) of the inventive method can be shown in the following formula:
其中
本发明的米格列醇纯度的间接测试法，由于首先将米格列醇酯化衍生，从而消除了分子键的氢键作用，因此能显著改善其挥发度，以便于进行定量分析(气相色谱检测)。测试步骤可按下述方案进行：取酯化反应液作为样品直接进气相色谱仪检测，得到的谱图中除去羧酸、酸酐以及吡啶这些轻组份的峰后进行归一化，即可得知米格列醇的纯度。The indirect test method of Miglitol purity of the present invention, because at first Miglitol is derivatized by esterification, thereby eliminated the hydrogen bond action of molecular bond, therefore can significantly improve its volatility, so that carry out quantitative analysis (gas chromatography detection). The test procedure can be carried out according to the following scheme: take the esterification reaction solution as a sample and directly detect it with a gas chromatograph, remove the peaks of light components such as carboxylic acid, acid anhydride and pyridine in the obtained spectrum, and then normalize. Know the purity of miglitol.
综上所述，本发明的米格列醇纯度的间接测试法，利用气相色谱检测法进行定量分析，利用衍生法能有效提高米格列醇挥发度而在GC中被检测到的性质，解决了米格列醇不能采用GC法检测的问题。In summary, the indirect test method of Miglitol purity of the present invention utilizes gas chromatography detection method to carry out quantitative analysis, utilizes derivatization method to effectively improve Miglitol volatility and the character that is detected in GC, solves Solved the problem that miglitol could not be detected by GC method.
本发明的米格列醇纯度的间接测试法，其特点在于：以低成本、高灵敏度的气相色谱法，替代了原有的高成本、低灵敏度视差折光检测器的液相色谱。因此，本发明具有测试方法简单、测试结果准确的特点。The indirect test method for the purity of miglitol of the present invention is characterized in that the gas chromatography with low cost and high sensitivity replaces the liquid chromatography of the original high cost and low sensitivity parallax refraction detector. Therefore, the present invention has the characteristics of simple test method and accurate test result.
将本发明在步骤1)所得的米格列醇全酯化衍生物[即含有乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯的酯化反应液或者含有丙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯的酯化反应液]进行提取，可得到浅灰色粉末状的乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯[或者是丙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯]。提取方法为：将酯化反应液减压脱轻组分(生成的羧酸、未反应完的酸酐、未反应完的催化剂无水吡啶)至糖浆状，加入2～5倍体积量去离子水，室温下静置1～2h析出固体，减压过滤，水洗，固体50℃烘干。The Miglitol full esterification derivative obtained in step 1) of the present invention [that is, containing acetic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)- The esterification reaction solution of ethyl ester or the esterification reaction solution containing propionic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester] is extracted, Acetic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester [or propionic acid-β-(3,4 , 5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester]. The extraction method is: decompress the esterification reaction liquid to remove light components (generated carboxylic acid, unreacted anhydride, unreacted catalyst anhydrous pyridine) to syrup, add 2 to 5 times the volume of deionized water , standing at room temperature for 1 to 2 hours to precipitate a solid, filter under reduced pressure, wash with water, and dry the solid at 50°C.
附图说明 Description of drawings
下面结合附图对本发明的具体实施方式作进一步详细说明。The specific implementation manners of the present invention will be described in further detail below in conjunction with the accompanying drawings.
图1是本发明的乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯(即五乙酸米格列醇酯)的H-NMR以及其中所采用的原子编号图。Fig. 1 is the H- NMR with atomic numbering diagrams employed therein.
图2是本发明的丙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯(即五丙酸米格列醇酯)的H-NMR以及其中所采用的原子编号图。Fig. 2 is propionic acid-beta-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester (i.e. miglitol pentapropionate) of the present invention H-NMR and the atomic numbering diagrams used therein.
具体实施方式 Detailed ways
实施例1、一种米格列醇纯度的间接测试法，包括以下步骤：Embodiment 1, a kind of indirect test method of Miglitol purity, comprises the following steps:
1)、50ml三口瓶中加入1.86g待测米格列醇白色粉末(为纯品)，17ml醋酐，1ml无水吡啶，机械搅拌，空气冷凝管回流，控制加热温度93～97℃，反应2h后停止反应，得含有乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯的酯化反应液(大约为20～25ml)。1) Add 1.86g of Miglitol white powder to be tested (pure product), 17ml of acetic anhydride, 1ml of anhydrous pyridine into a 50ml three-necked flask, stir mechanically, reflow the air condenser, control the heating temperature to 93-97°C, and react After 2 hours, the reaction was stopped to obtain an esterification reaction solution containing acetic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester (about 20-25ml) .
2)、对上述酯化反应液直接取样进行检测，所用气相色谱仪配套氢火焰监测器以及程序升温，得到含有乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯、轻组分(生成的乙酸、未反应完的醋酐、未反应完的催化剂无水吡啶)的气相色谱图，除去轻组分后对峰面积进行归一化处理，从而得知乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯质量百分含量为99.9％，没有其他杂质。由于米格列醇全部转变成了乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯，推算得米格列醇纯度为99.9％。2), the above-mentioned esterification reaction solution is directly sampled and detected, and the gas chromatograph used is equipped with a hydrogen flame monitor and a temperature program to obtain Base-1-piperidine)-ethyl ester, light components (acetic acid generated, unreacted acetic anhydride, unreacted catalyst anhydrous pyridine), the peak area is normalized after removing the light components After chemical treatment, it is known that the mass percentage of acetic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester is 99.9%, and there are no other impurities. Since Miglitol is completely transformed into acetic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester, the purity of Miglitol is estimated to be 99.9% %.
推算方法如下：The calculation method is as follows:
将乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯的质量百分含量换算为摩尔百分含量，此摩尔百分含量与待测样品中米格列醇的摩尔百分含量一致，得到了摩尔百分含量，再将其换算为质量百分含量，即为样品米格列醇纯度。The mass percentage of acetic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester is converted into mole percentage, and this mole percentage is the same as The mole percentage of miglitol in the samples to be tested is the same, and the mole percentage is obtained, and then converted into mass percentage, which is the purity of the sample miglitol.
待测米格列醇样实际纯度为100％，测试准确度为99.9％。The actual purity of the miglitol sample to be tested is 100%, and the test accuracy is 99.9%.
将完全同实施例1的步骤1)所述方法获得的含有乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯的酯化反应液进行提取，提取方法如下：The esterification of acetic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester obtained by the method described in step 1) of Example 1 The reaction solution is extracted, and the extraction method is as follows:
将该酯化反应液减压脱轻组分(生成的乙酸、未反应完的酸酐、未反应完的催化剂无水吡啶)至糖浆状，加入2～5倍体积量的去离子水，室温下静置1～2h，析出固体，减压过滤，水洗，固体50℃烘干。所得固体经HNMR检测，证明其结构为乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯，HNMR图谱及其原子编号图如图1所示，图1中：The esterification reaction solution is decompressed to remove light components (generated acetic acid, unreacted anhydride, unreacted catalyst anhydrous pyridine) to syrup, add 2 to 5 times the volume of deionized water, and Stand still for 1-2 hours, the solid precipitates, filter under reduced pressure, wash with water, and dry the solid at 50°C. The resulting solid is detected by HNMR, and its structure is proved to be acetic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester, and the HNMR spectrum and its atomic number are shown in As shown in Figure 1, in Figure 1:
HNMR(400MHz，d6-DMSO)：4.99～5.04(t，1H，4-H)，4.83～4.88(t，1H，5-H)，4.75～4.81(m，1H，3-H)，4.03～4.17(m，4H，8-2H，21-2H)，3.09～3.13(t，1H，6-H)，2.83～3.00(m，3H，2-H，7-2H)，2.58～2.64(t，1H，2-H)，2.01(s，3H，CH3)，2.00(s，3H，CH3)，1.99(s，3H，CH3)，1.98(s，3H，CH3)，1.96(s，3H，CH3)HNMR (400MHz, d 6 -DMSO): 4.99～5.04(t, 1H, 4-H), 4.83～4.88(t, 1H, 5-H), 4.75～4.81(m, 1H, 3-H), 4.03 ～4.17(m, 4H, 8-2H, 21-2H), 3.09～3.13(t, 1H, 6-H), 2.83～3.00(m, 3H, 2-H, 7-2H), 2.58～2.64( t, 1H, 2-H), 2.01 (s, 3H, CH 3 ), 2.00 (s, 3H, CH 3 ), 1.99 (s, 3H, CH 3 ), 1.98 (s, 3H, CH 3 ), 1.96 (s, 3H, CH3 )
结构式如式1：The structural formula is as formula 1:
(式1)(Formula 1)
实施例2、一种米格列醇纯度的间接测试法，包括以下步骤：Embodiment 2, a kind of indirect test method of Miglitol purity, comprises the following steps:
1)、50ml三口瓶中加入1.86g待测的米格列醇白色粉末(由1.60g纯品米格列醇+0.26g山梨醇组成)，20ml醋酐，机械搅拌，空气冷凝管回流，控制加热温度93～97℃，反应2h，停止反应，得含有乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯(结构式如式1)的酯化反应液。1) Add 1.86g of Miglitol white powder to be tested (composed of 1.60g of pure Miglitol + 0.26g of sorbitol) into a 50ml three-necked bottle, 20ml of acetic anhydride, stir mechanically, and reflux the air condenser to control Heating temperature is 93～97°C, react for 2 hours, stop the reaction, and obtain acetic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester (structural formula is as follows: 1) The esterification reaction solution.
2)、对上述酯化反应液直接取样进行检测，所用气相色谱仪配套氢火焰监测器以及程序升温，得到含有乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯、以及杂质(山梨醇酯化物)、轻组分(包括生成的乙酸、未反应完的醋酐)的气相色谱图。除去轻组分后对峰面积进行归一化处理，得出乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯质量百分含量为84.7％，由于米格列醇全部转变成了乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯，推算得米格列醇纯度为86.7％。2), the above-mentioned esterification reaction solution is directly sampled and detected, and the gas chromatograph used is equipped with a hydrogen flame monitor and a temperature program to obtain Base-1-piperidine)-ethyl ester, and impurity (sorbitol ester), light components (including acetic acid generated, unreacted acetic anhydride) gas chromatogram. After removing the light component, the peak area is normalized to obtain the mass percentage of acetic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester The content is 84.7%. Since Miglitol is completely transformed into acetic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester, it is estimated that Miglitol The purity of column alcohol is 86.7%.
待测米格列醇样实际纯度为86.0％，测试准确度为99.2％。The actual purity of the miglitol sample to be tested was 86.0%, and the test accuracy was 99.2%.
实施例3、一种米格列醇纯度的间接测试法，将实施例2中的1.86g待测的米格列醇白色粉末改成由1.50g纯品米格列醇+0.36g山梨醇组成，其余内容同实施例2；所得结果如下：Embodiment 3, an indirect test method of the purity of Miglitol, the 1.86g white powder of Miglitol to be tested in Example 2 is changed to be composed of 1.50g pure Miglitol+0.36g sorbitol , all the other contents are with embodiment 2; Gained result is as follows:
乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯质量百分含量为78.6％，由于米格列醇全部转变成了乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯，推算得米格列醇纯度为81.2％。Acetate-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester mass percentage content is 78.6%, because miglitol is all converted into acetic acid- β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester, the calculated purity of miglitol was 81.2%.
待测米格列醇样实际纯度为80.6％，测试准确度为99.3％。The actual purity of the miglitol sample to be tested was 80.6%, and the test accuracy was 99.3%.
实施例4、一种米格列醇纯度的间接测试法，依次进行以下步骤：Embodiment 4, a kind of indirect test method of Miglitol purity, carries out following steps successively:
1)、50ml三口瓶中加入2.17g米格列醇白色粉末(为纯品)，22ml丙酸酐，1ml无水吡啶，机械搅拌，空气冷凝管回流，控制加热温度93～97℃，反应2.5h，停止反应，得含有丙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯的酯化反应液。1) Add 2.17g of miglitol white powder (pure product), 22ml of propionic anhydride, 1ml of anhydrous pyridine into a 50ml three-necked bottle, stir mechanically, reflux the air condenser, control the heating temperature to 93-97°C, and react for 2.5h , Stop the reaction to obtain an esterification reaction solution containing propionic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester.
2)、对上述酯化反应液直接取样进行检测，所用气相色谱仪配套氢火焰监测器以及程序升温，得到含有丙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯、轻组分(生成的丙酸、未反应完的丙酸酐、未反应完的催化剂无水吡啶)的气相色谱图，除去轻组分后对峰面积进行归一化处理，从而得知丙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯质量百分含量为99.9％。由于米格列醇全部转变成了丙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯，推算得米格列醇纯度为99.9％。2), the above-mentioned esterification reaction solution is directly sampled and detected, and the gas chromatograph used is equipped with a hydrogen flame monitor and a temperature program to obtain a mixture containing propionic acid-β-(3,4,5-triacetoxy-2-acetoxy The gas chromatogram of methyl-1-piperidine)-ethyl ester, light components (propionic acid generated, unreacted propionic anhydride, unreacted catalyst anhydrous pyridine), after removing the light components, the peak area Normalization processing is carried out, so that the mass percentage content of propionic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester is 99.9%. Since miglitol has all been converted into propionic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester, the purity of miglitol is estimated to be 99.9%.
待测米格列醇样实际纯度为100％，测试准确度为99.9％。The actual purity of the miglitol sample to be tested is 100%, and the test accuracy is 99.9%.
同样，将完全同实施例4的步骤1)所述方法获得的含有丙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯的酯化反应液进行提取方法，提取方法同上，所得固体经HNMR检测，证明其结构为丙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯，其HNMR谱图以及原子编号图如图2所示，图2中：Similarly, the method obtained in step 1) of Example 4 containing propionic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl The extraction method of the esterification reaction solution is the same as above, and the obtained solid is detected by HNMR, which proves that its structure is propionic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piper Pyridine)-ethyl ester, its HNMR spectrogram and atomic numbering figure are as shown in Figure 2, in Figure 2:
HNMR(400MHz，d6-DMSO)：5.14～5.16(t，1H，4-H)，4.51～4.59(m，2H，3-H，5-H)，4.16～4.28(m，3H，8-2H，21-H)，3.99～4.02(d，1H，21-H)，3.40～3.43(m，1H，6-H)，2.58～2.66(m，3H，2-H，7-2H)，2.33～2.39(t，1H，2-H)，2.25～2.31(q，10H，5CH2)，1.10～1.17(t，15H，5CH3)HNMR (400MHz, d 6 -DMSO): 5.14～5.16(t, 1H, 4-H), 4.51～4.59(m, 2H, 3-H, 5-H), 4.16～4.28(m, 3H, 8- 2H, 21-H), 3.99～4.02(d, 1H, 21-H), 3.40～3.43(m, 1H, 6-H), 2.58～2.66(m, 3H, 2-H, 7-2H), 2.33～2.39(t, 1H, 2-H), 2.25～2.31(q, 10H, 5CH 2 ), 1.10～1.17(t, 15H, 5CH 3 )
结构式如式2所示：The structural formula is as shown in formula 2:
(式2)(Formula 2)
实施例5、一种米格列醇纯度的间接测试法，将实施例4中的2.17g待测的米格列醇改成由1.91g纯品米格列醇+0.26g山梨醇组成，其余内容同实施例4；所得结果如下：
丙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯量百分含量为86.3％，由于米格列醇全部转变成了乙酸-β-(3，4，5-三乙酰氧基-2-乙酰氧甲基-1-哌啶)-乙酯，推算得米格列醇纯度为88.4％。The percentage content of propionic acid-β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester was 86.3%, because miglitol was completely converted into acetic acid -β-(3,4,5-triacetoxy-2-acetoxymethyl-1-piperidine)-ethyl ester, the calculated purity of miglitol is 88.4%.
待测米格列醇样实际纯度为88.0％，测试准确度为99.5％。The actual purity of the miglitol sample to be tested was 88.0%, and the testing accuracy was 99.5%.
最后，还需要注意的是，以上列举的仅是本发明的若干个具体实施例。显然，本发明不限于以上实施例，还可以有许多变形。本领域的普通技术人员能从本发明公开的内容直接导出或联想到的所有变形，均应认为是本发明的保护范围。Finally, it should be noted that the above examples are only some specific embodiments of the present invention. Obviously, the present invention is not limited to the above embodiments, and many variations are possible. All deformations that can be directly derived or associated by those skilled in the art from the content disclosed in the present invention should be considered as the protection scope of the present invention.
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100961915A CN101487827B (en) | 2009-02-19 | 2009-02-19 | Indirect Test Method for Miglitol Purity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100961915A CN101487827B (en) | 2009-02-19 | 2009-02-19 | Indirect Test Method for Miglitol Purity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101487827A true CN101487827A (en) | 2009-07-22 |
| CN101487827B CN101487827B (en) | 2011-11-23 |
Family
ID=40890799
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009100961915A Expired - Fee Related CN101487827B (en) | 2009-02-19 | 2009-02-19 | Indirect Test Method for Miglitol Purity |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101487827B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104693109A (en) * | 2013-12-05 | 2015-06-10 | 陕西师范大学 | A preparing method of a miglitol intermediate |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100580446C (en) * | 2008-04-10 | 2010-01-13 | 常熟市联邦化工有限公司 | Method for testing pyromellitic acid anhydride purity and organic impurity |
-
2009
- 2009-02-19 CN CN2009100961915A patent/CN101487827B/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104693109A (en) * | 2013-12-05 | 2015-06-10 | 陕西师范大学 | A preparing method of a miglitol intermediate |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101487827B (en) | 2011-11-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ding et al. | A selective pretreatment method for determination of endogenous active brassinosteroids in plant tissues: double layered solid phase extraction combined with boronate affinity polymer monolith microextraction | |
| Hu et al. | Interaction between amylose and 1-butanol during 1-butanol-hydrochloric acid hydrolysis of normal rice starch | |
| Ren et al. | High performance liquid chromatography‐mass spectrometry analysis of protoberberine alkaloids in medicine herbs | |
| Li et al. | A new application of acetylation for analysis of acidic heteropolysaccharides by liquid chromatography-electrospray mass spectrometry | |
| CN101487827A (en) | Indirect test method for Miglitol purity | |
| CN110441446B (en) | Method for effectively detecting purity of 2-chloropropionyl chloride | |
| CN107478755A (en) | Method for preparing purified for the crystal methamphetamine standard substance of forensic science illicit drugs inspection | |
| CN109142586B (en) | Method for determining content of atorvastatin calcium intermediate ATS-9 and impurity B thereof by liquid chromatography | |
| CN113533574B (en) | Composition for drug synthesis and detection method of p-toluenesulfonyl chloride in composition | |
| Holder et al. | Mass spectral characterization of doxylamine and its rhesus monkey urinary metabolites | |
| CN102863379A (en) | Analytical reagent for measuring heavy metal and method for preparing same | |
| CN100580446C (en) | Method for testing pyromellitic acid anhydride purity and organic impurity | |
| CN101487828A (en) | Detection method for isocyanuric acid three-glycidyl ester | |
| Bieri et al. | Use of porous graphitic carbon column for the separation of natural isomeric tropane alkaloids by capillary LC and mass spectrometry | |
| CN103018389B (en) | High performance liquid chromatography method and application thereof | |
| CN112578038B (en) | Analysis and detection method for berberine hydrochloride bulk drug | |
| Dehennin et al. | Dienol heptafluorobutyrates as derivatives for gas liquid chromatography of steroidal Δ4-3-ketones: Determination of the structure of the isomeric dienol esters | |
| CN102183593B (en) | Method for detecting mannitol content of cordyceps hawkesii | |
| CN101832980A (en) | Method for measuring di-ethylhexyl maleate in food packaging material | |
| CN108558964B (en) | Purification method of α -arbutin | |
| CN102901788B (en) | Liquid chromatography-mass spectrum detection method for lutein disuccinate | |
| CN102304164A (en) | Senegenin derivative, as well as preparation method and application thereof | |
| CN106661040A (en) | 6-aryl amino pyridone formamide compound crystal and preparation method therefor | |
| CN108047221B (en) | A perylene diimide compound, its synthesis method and its application in H2O2 detection | |
| CN102584759A (en) | Extraction method for costunolide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20111123 Termination date: 20120219 |