WO2022156241A1 - 苯佐那酯中有关物质mpeg的检测方法 - Google Patents
苯佐那酯中有关物质mpeg的检测方法 Download PDFInfo
- Publication number
- WO2022156241A1 WO2022156241A1 PCT/CN2021/118400 CN2021118400W WO2022156241A1 WO 2022156241 A1 WO2022156241 A1 WO 2022156241A1 CN 2021118400 W CN2021118400 W CN 2021118400W WO 2022156241 A1 WO2022156241 A1 WO 2022156241A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- benzonatate
- mpeg
- solution
- detection method
- sample
- Prior art date
Links
- 229960003789 benzonatate Drugs 0.000 title claims abstract description 46
- 238000000034 method Methods 0.000 title claims abstract description 27
- 239000000126 substance Substances 0.000 title claims abstract description 21
- MAFMQEKGGFWBAB-UHFFFAOYSA-N benzonatate Chemical compound CCCCNC1=CC=C(C(=O)OCCOCCOCCOCCOCCOCCOCCOCCOCCOC)C=C1 MAFMQEKGGFWBAB-UHFFFAOYSA-N 0.000 title claims abstract 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 57
- 238000001514 detection method Methods 0.000 claims abstract description 47
- 239000000243 solution Substances 0.000 claims abstract description 21
- 239000000523 sample Substances 0.000 claims abstract description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000012488 sample solution Substances 0.000 claims abstract description 16
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 15
- 238000000105 evaporative light scattering detection Methods 0.000 claims abstract description 13
- 239000011259 mixed solution Substances 0.000 claims abstract description 6
- 239000012086 standard solution Substances 0.000 claims abstract description 5
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 12
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 6
- 235000019253 formic acid Nutrition 0.000 claims description 6
- 238000002347 injection Methods 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 238000011895 specific detection Methods 0.000 abstract description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 34
- YCCRFDDXAVMSLM-UHFFFAOYSA-N 4-(butylamino)benzoic acid Chemical compound CCCCNC1=CC=C(C(O)=O)C=C1 YCCRFDDXAVMSLM-UHFFFAOYSA-N 0.000 description 25
- 239000000203 mixture Substances 0.000 description 7
- 238000011084 recovery Methods 0.000 description 6
- 239000012224 working solution Substances 0.000 description 6
- 239000003085 diluting agent Substances 0.000 description 5
- 239000002994 raw material Substances 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- 206010011224 Cough Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 239000003434 antitussive agent Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012490 blank solution Substances 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
Definitions
- the invention relates to a detection method for related substances in medicines, belongs to the technical field of analytical chemistry, and in particular relates to a detection method for related substances MPEG in benzonatate.
- Benzonatate was developed by Pfizer and approved for sale by the U.S. Food and Drug Administration on February 10, 1958. It is a non-narcotic oral cough suppressant with a 6-8 hour duration after delivery of the immediate-release composition. Therapeutic effect, its official name is 2, 5, 8, 11, 14, 17, 20, 23, 26-nonaoxacosa-28-yl p-butylaminobenzoate. Because it is not an opioid, like some other cough medicines such as codeine, benzonatate is not easily abused.
- MPEG is the initial material for synthesizing benzonatate, so the detection of MPEG content in finished benzonatate is one of the important items in process exploration and raw material quality research.
- the Chinese name of MPEG is polyethylene glycol monomethyl ether, and its molecular structure is as follows:
- the present invention discloses a method for detecting MPEG, a related substance in benzonatate.
- the detection method can not only quickly and accurately detect the MPEG content of the related substance in benzonatate, but also has a low detection limit, and is suitable for mass detection of samples in the actual production process.
- the present invention discloses a method for detecting MPEG, a related substance in benzonatate, which is a high performance liquid chromatography combined with an evaporative light scattering detection method.
- the chromatographic column is SUPELCO SUPLEX PKB-100 250 ⁇ 4.6mm, 5um;
- the mobile phase includes a mobile phase formed by mixing acetonitrile and water; formic acid is also added to the mobile phase, and the amount of formic acid added is 0.005-0.02% of the mobile phase volume;
- the evaporative light scattering detector conditions are as follows:
- Atomizer power 65 ⁇ 75%
- Drift tube temperature 50 ⁇ 110°C
- Gain gradient 0 ⁇ 4.5min, 300 ⁇ 100Gain
- the detection method includes the following processes:
- step 3 utilize high performance liquid chromatography to measure the peak area of the benzonatate sample solution in step 2), and then obtain the concentration of MPEG in the benzonatate sample solution corresponding to the standard curve described in step 1);
- step 1) chromatographic conditions of step 1) and step 3) are the same.
- volume ratio of acetonitrile to water in the mobile phase is (40-60):(60-40), and the flow rate of the mobile phase is 0.5-2 mL/min.
- the column temperature of the chromatographic column is 25 ⁇ 2° C.
- the temperature of the sample chamber is 10° C.
- the injection volume is 20-100 ⁇ L.
- the column temperature of the chromatographic column is 25° C., and the injection volume is 20 ⁇ L.
- the concentration of the MPEG standard solution is 0.0036-0.36 mg/mL.
- the MPEG of the present invention is MPEG-420.
- the concentration of the benzonatate sample solution in step 2) is 10-70 mg/mL.
- step 2) the volume ratio of acetonitrile and water in the mixed solution is (40-60):(60-40).
- the detection method further includes preparing an MPEG control solution, and the concentration of the MPEG control solution is 0.036-0.144 mg/mL.
- the detection method designed by the invention can not only quickly and accurately detect the MPEG content of the related substance in benzonatate, but also has a detection limit as low as 0.004 mg/mL, and high accuracy and precision.
- the detection method is suitable for the actual production process. Large batch detection of samples.
- Fig. 1 is the chromatogram of the diluent selected by the present invention
- Fig. 2 is the chromatogram of control solution
- Fig. 3 is the chromatogram of benzonatate sample
- Figure 4 is a chromatogram of a 100% spiked sample.
- the invention discloses a detection method for related substances MPEG in benzonatate. method.
- this detection method can not only quickly and accurately determine the MPEG content in benzonatate raw materials, but also stably, and at the same time, the minimum detection limit can reach 0.004mg/ mL, where the minimum detection limit is equivalent to a sample mass percentage concentration of 0.02%; the detection method is suitable for large-scale detection of samples in the actual production process.
- the detection method of the present invention relates to the detection instrument used and the relevant model as follows:
- Evaporative light scattering detector Waters 2424 ELS detector
- the MPEG stock solution with a concentration of 0.36 mg/mL accurately weigh 36 mg of MPEG standard product to a 100 mL volumetric flask, dissolve it with a mixture of diluent acetonitrile and water, and adjust the volume to the mark, wherein, in the mixture, acetonitrile and The volume ratio of water is (40 ⁇ 60):(60 ⁇ 40).
- the present invention preferably adopts a mixed solution with a volume ratio of acetonitrile and water of 50:50 as a diluent for dilution.
- the above-mentioned MPEG stock solution is diluted to obtain a series of standard working solutions with a concentration of 0.0036 to 0.36 mg/mL, and the concentration of each standard working solution is shown in Table 1:
- Injection volume 20 ⁇ 100 ⁇ L
- Atomizer power 65 ⁇ 75%
- Drift tube temperature 50 ⁇ 110°C
- Gain gradient 0 ⁇ 4.5min, 300 ⁇ 100Gain
- the present invention also screens chromatographic conditions and evaporative light scattering detection conditions to obtain the following Table 2;
- the blank solution does not have any interference peaks at the MPEG retention time; and the control solution spectrum with a concentration of 0.072mg/mL obtained by the above-mentioned detection method is shown in Figure 2, and the concentration is 24mg/mL Benzonatate sample
- the solution spectrum is shown in Figure 3, and the 100% spiked sample solution spectrum is shown in Figure 4.
- the control solution has no interference peak at the MPEG retention time, and the MPEG peak shape is normal. The MPEG peak and the adjacent peaks in the solution were well separated, and the MPEG peak shape was normal.
- step (1) preparation is 0.0036mg/mL, measure according to above-mentioned detection method, calculate accuracy and precision, and wherein accuracy is as shown in Table 3;
- the solution was prepared in triplicate according to Table 5, and the recovery rate was determined, as shown in Table 6.
- the sample solution and the control solution under the precision item were placed at room temperature for 72h and refrigerated for 72h to determine the MPEG content
- the detection method designed in the present invention has high accuracy and precision, and the lower detection limit is as low as 0.004 mg/mL, which is suitable for large-scale detection of samples in the actual production process.
Landscapes
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
Abstract
本发明公开了一种苯佐那酯中有关物质MPEG的检测方法，该检测方法为高效液相色谱联合蒸发光散射检测法，具体检测过程包括1)配制不同浓度的MPEG标准溶液，利用高效液相色谱法建立MPEG溶液浓度与峰面积的标准曲线；2)取苯佐那酯样品溶解至乙腈和水的混合液中制备得到苯佐那酯样品溶液；3)利用高效液相色谱法测定步骤2)中苯佐那酯样品溶液的峰面积，然后对应步骤1)中标准曲线得到苯佐那酯样品溶液中MPEG的浓度；该检测方法不仅能快速准确的测出苯佐那酯中有关物质MPEG含量，同时检测限低，适用于实际生产过程中样本的大批量检测。
Description
本发明涉及一种药品中有关物质的检测方法，属于分析化学技术领域，具体地涉及一种苯佐那酯中有关物质MPEG的检测方法。
苯佐那酯由辉瑞研发，并于1958年2月10日获美国食品药品监督管理局批准上市销售，其属于非麻醉性口服咳嗽遏制剂，具有递送速释组合物后持续6～8小时的治疗效果，其正式名称为2，5，8，11，14，17，20，23，26-九氧杂二十八烷-28-基对丁基氨基苯甲酸酯。由于它不是阿片样物质，因此像一些其他咳嗽药例如可待因一样，苯佐那酯不易被滥用。
MPEG是合成苯佐那酯的初始物料，因此检测成品苯佐那酯中MPEG含量是工艺探究及原料质量研究中的重要项目之一。
MPEG的中文名称为聚乙二醇单甲醚，分子结构式如下：
现有检测苯佐那酯原料中MPEG杂质常采用质谱法，但是实验室配置率较低，导致之后多为送检方式，检测周期长、检测准确度不高且检测时间不可控，这对于指导苯佐那酯的实际生产十分不利。
发明内容
为解决上述技术问题，本发明公开了一种苯佐那酯中有关物质MPEG的检测方法。该检测方法不仅能快速准确的测出苯佐那酯中有关物质MPEG含量，同时检测限低，适用于实际生产过程中样本的大批量检测。
为实现上述目的，本发明公开了一种苯佐那酯中有关物质MPEG的检测方法，所述检测方法为高效液相色谱联合蒸发光散射检测法。
进一步地，所述高效液相色谱条件如下：
色谱柱为SUPELCO SUPLEX PKB-100 250×4.6mm,5um；
流动相包括乙腈和水混合而成的流动相；所述流动相中还加入甲酸，且所述甲酸的加入量为流动相体积的0.005～0.02％；
所述蒸发光散射检测器条件如下：
雾化器功率：65～75％；
漂移管温度：50～110℃；
气体压力：10～50psi；
增益梯度：0～4.5min，300～100Gain；
4.5～25min，100～50Gain；
该检测方法包括如下过程：
1)配制不同浓度的MPEG标准溶液，利用高效液相色谱法建立MPEG溶液浓度与峰面积的标准曲线；
2)取苯佐那酯样品溶解至乙腈和水的混合液中制备得到苯佐那酯样品溶液；
3)利用高效液相色谱法测定步骤2)中苯佐那酯样品溶液的峰面积，然后对应步骤1)中所述标准曲线得到苯佐那酯样品溶液中MPEG的浓度；
且步骤1)和步骤3)的色谱条件相同。
进一步地，所述蒸发光散射检测器的增益梯度：
0～4.5min，200～100Gain；
4.5～25min，100～50Gain。
进一步地，所述流动相中乙腈与水的体积比为(40～60):(60～40)，且所述流动相流速为0.5～2mL/min。
进一步地，所述色谱柱柱温为25±2℃，样品室温度为10℃，进样量为20～100μL。
进一步地，所述色谱柱柱温为25℃，所述进样量为20μL。
进一步地，步骤1)中，所述MPEG标准溶液的浓度为0.0036～0.36mg/mL。优选的，本发明的MPEG为MPEG-420。
进一步地，步骤2)中所述苯佐那酯样品溶液浓度为10～70mg/mL。
进一步地，步骤2)中，所述混合液中乙腈和水的体积比为(40～60):(60～40)。
进一步地，所述检测方法还包括制备MPEG对照溶液，所述MPEG对照溶液浓度为0.036～0.144mg/mL。
本发明设计的检测方法不仅能快速准确的测出苯佐那酯中有关物质MPEG含量，同时检测限低至0.004mg/mL，准确度和精密度较高，该检测方法适用于实际生产过程中样本的大批量检测。
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据提供的附图获得其他的附图。
图1为本发明选择的稀释剂的色谱图；
图2为对照溶液的色谱图；
图3为苯佐那酯样品的色谱图；
图4为100％加标样品的色谱图。
本发明为解决现有技术检测苯佐那酯原料中相关物质的手段准确度不高，检测周期长，以及检测时间不可控的技术问题，公开了一种苯佐那酯中有关物质MPEG的检测方法。该检测方法通过将高效液相色谱法与蒸发光散射检测法联合在一起使用，不仅能够快速准确的，并且稳定的测定苯佐那酯原料中MPEG含量，同时，最低检测限可达到0.004mg/mL，其中该最低检测限相当于样品质量百分比浓度为0.02％；该检测方法适用于实际生产过程中样本的大批量检测。
1、本发明检测方法涉及使用的检测仪器及相关型号如下：
分析天平：梅特勒；
移液器：Brand移液管
高效液相色谱系统：Waters e2695；
蒸发光散射检测器：Waters 2424 ELS检测器；
2、具体检测过程如下：
(1)标准工作溶液的配制：
首先配制浓度为0.36mg/mL的MPEG储备液：精密称取MPEG标准品36mg至100mL容量瓶，用稀释剂乙腈与水的混合液溶解并定容至刻度，其中，所述混合液中乙腈与水的体积比为(40～60):(60～40)。本发明优选采用乙腈与水的体积比为50:50的混合液作为稀释剂进行稀释。
具体的对上述MPEG储备液进行稀释，得到浓度为0.0036～0.36mg/mL的系列标准工作液，且各标准工作液的浓度如表1所示：
表1标准工作液浓度列表
(2)苯佐那酯样品的处理：
取苯佐那酯样品240mg溶解至乙腈和水的混合液中，并继续定容至10mL容量瓶中，其中，所述混合液中乙腈和水的体积比为50:50，制备得到浓度为24mg/mL的苯佐那酯样品溶液。
(3)制备对照溶液：
精密称取MPEG标准品3.6mg至100mL、50mL、25mL容量瓶，用稀 释剂乙腈与水的混合液溶解并定容至刻度，其中，本发明优选采用乙腈与水的体积比为50:50的混合液作为稀释剂进行稀释。得到所述MPEG对照溶液浓度为0.036～0.144mg/mL。
(4)高效液相色谱联合蒸发光散射检测法工作条件为：
(4.1)色谱条件：
色谱柱：SUPELCO SUPLEX PKB-100 250*4.6mm,5um；
流动相：乙腈/水/甲酸(v/v＝(40～60):(60～40)，甲酸的加入量为流动相体积的0.005～0.02％)；
洗针液：乙腈/水(v/v＝(40～60):(60～40))；
流速：0.5～2.0mL/min；
柱温：25±2℃；
样品室温度：10℃；
进样量：20～100μL；
样品运行时间：20～40min；
对照样运行时间：8min；
(4.2)蒸发光散射检测条件：
气体压力：10～50psi；
雾化器功率：65～75％；
漂移管温度：50～110℃；
增益梯度：0～4.5min，300～100Gain；
4.5～25min，100～50Gain；
同时，本发明还对色谱条件及蒸发光散射检测条件进行筛选，得到如下表2；
表2检测条件筛选列表
(5)分析结果：
利用高效液相色谱法建立步骤(1)中MPEG标准工作溶液与峰面积的标准曲线；且标准曲线为y＝1.346x+6515(R
2＝0.9948，R＝0.997)，由该标准曲线可知最低检测限可达到0.004mg/mL，其中该最低检测限相当于样品质量百分比浓度为0.02％，同时在样品质量百分比浓度0.03～150％范围内，线性良好。
由图1可知，空白溶液在MPEG保留时间处无任何干扰峰；并且采用上述检测方法得到浓度为0.072mg/mL的对照溶液图谱如图2所示，浓度为24mg/mL的苯佐那酯样品溶液图谱如图3所示，100％加标样品溶液图谱如图4所示，由图2可知对照溶液在MPEG保留时间处无干扰峰，MPEG峰型正常，由图3及图4可知，样品溶液中MPEG峰与相邻峰分离度良好，MPEG峰型正常。
(6)准确度及精密度评价：
取步骤(1)配制的浓度为0.0036mg/mL的MPEG标准工作溶液各6份，按照上述检测方法测定，计算准确度和精密度，其中准确度如表3所示；
表3准确度评价表
| 样品 | 峰面积 | MPEG含量％ |
| 1 | 2614 | 0.054％ |
| 2 | 2619 | 0.054％ |
| 3 | 2670 | 0.055％ |
| 4 | 2459 | 0.051％ |
| 5 | 2380 | 0.052％ |
| 6 | 2119 | 0.049％ |
| 平均值 | 2477 | 0.05％ |
| RSD％(n＝6) | 8.4％ | 4.3％ |
由表3可知，本发明设计的检测方法精密度良好。
另一分析人员在不同时间，使用不同色谱柱，按照精密度方法测定上述6个样品。结果如表3所示；
表4精密度评价表
由表4可知，即使是不同分析人员采用不同色谱柱，精密度测定方法的测量结果一致，这再次说明该方法重现性良好。
(7)待测物提取回收率：
利用上述制备的浓度为0.36mg/mL的MPEG标准储备液按照下表5配置溶液一式三份，并测定回收率，如表6所示。
表5加标样品浓度列表
表6加标样品回收率列表(一)
在原方法基础上改变色谱条件，分别测定其回收率。
色谱条件改变分别为：
流速±0.1mL/min；
柱温+5℃；
流动相中乙腈比例：±1％；
结果如表7所示：
表7加标样品回收率列表(二)
由上述表5～表6可知，回收率合格，这说明本发明设计的测量方法准确度高，测量值与真实值接近程度高。
由表7可知，在一定程度上稍微的改变柱温，流速，流动相比例情况 下验证该分析方法不受影响能力。这说明该分析方法耐用性较强。
(8)样品稳定性：
使用精密度项下样品溶液与对照溶液分别放置室温72h和冷藏72h测定MPEG含量
结果如表8和表9所示：
表8对照溶液稳定性列表
表9样品溶液稳定性列表
由上述表8～表9可知，对照溶液与样品溶液在室温与冷藏条件下72小时稳定。
由上述检测方法可知，本发明设计的检测方法准确度和精密度均较高，且检测下限低至0.004mg/mL，适用于实际生产过程中样本的大批量检测。
以上实施例仅为最佳举例，而并非是对本发明的实施方式的限定。除上述实施例外，本发明还有其他实施方式。凡采用等同替换或等效变换形成的技术方案，均落在本发明要求的保护范围。
Claims (10)
- 一种苯佐那酯中有关物质MPEG的检测方法，其特征在于，所述检测方法为高效液相色谱联合蒸发光散射检测法。
- 根据权利要求1所述苯佐那酯中有关物质MPEG的检测方法，其特征在于，所述高效液相色谱条件如下：色谱柱为SUPELCO SUPLEX PKB-100 250×4.6mm,5um；流动相包括乙腈和水混合而成的流动相；所述流动相中还加入甲酸，且所述甲酸的加入量为流动相体积的0.005～0.02％；所述蒸发光散射检测器条件如下：雾化器功率：65～75％；漂移管温度：50～110℃；气体压力：10～50psi；增益梯度：0～4.5min，300～100Gain；4.5～25min，100～50Gain；该检测方法包括如下过程：1)配制不同浓度的MPEG标准溶液，利用高效液相色谱法建立MPEG溶液浓度与峰面积的标准曲线；2)取苯佐那酯样品溶解至乙腈和水的混合液中制备得到苯佐那酯样品溶液；3)利用高效液相色谱法测定步骤2)中苯佐那酯样品溶液的峰面积，然后对应步骤1)中所述标准曲线得到苯佐那酯样品溶液中MPEG的浓度；且步骤1)和步骤3)的色谱条件相同。
- 根据权利要求2所述苯佐那酯中有关物质MPEG的检测方法，其特征在于，所述蒸发光散射检测器的增益梯度：0～4.5min，200～100Gain；4.5～25min，100～50Gain。
- 根据权利要求2所述苯佐那酯中有关物质MPEG的检测方法，其特征在于，所述流动相中乙腈与水的体积比为(40～60):(60～40)，且所 述流动相流速为0.5～2mL/min。
- 根据权利要求2～4中任意一项所述苯佐那酯中有关物质MPEG的检测方法，其特征在于，所述色谱柱柱温为25±2℃，样品室温度为10℃，进样量为20～100μL。
- 根据权利要求5所述苯佐那酯中有关物质MPEG的检测方法，其特征在于，所述色谱柱柱温为25℃，所述进样量为20μL。
- 根据权利要求2～4中任意一项所述苯佐那酯中有关物质MPEG的检测方法，其特征在于，步骤1)中，所述MPEG标准溶液的浓度为0.0036～0.36mg/mL。
- 根据权利要求2～4中任意一项所述苯佐那酯中有关物质MPEG的检测方法，其特征在于，步骤2)中所述苯佐那酯样品溶液浓度为10～70mg/mL。
- 根据权利要求8所述苯佐那酯中有关物质MPEG的检测方法，其特征在于，步骤2)中，所述混合液中乙腈和水的体积比为(40～60):(60～40)。
- 根据权利要求2～4中任意一项所述苯佐那酯中有关物质MPEG的检测方法，其特征在于，所述检测方法还包括制备MPEG对照溶液，所述MPEG对照溶液浓度为0.036～0.144mg/mL。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110098008.6A CN112903860B (zh) | 2021-01-25 | 2021-01-25 | 苯佐那酯中有关物质mpeg的检测方法 |
| CN202110098008.6 | 2021-01-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2022156241A1 true WO2022156241A1 (zh) | 2022-07-28 |
Family
ID=76119831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2021/118400 WO2022156241A1 (zh) | 2021-01-25 | 2021-09-15 | 苯佐那酯中有关物质mpeg的检测方法 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN112903860B (zh) |
| WO (1) | WO2022156241A1 (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112903860B (zh) * | 2021-01-25 | 2022-05-27 | 人福普克药业（武汉）有限公司 | 苯佐那酯中有关物质mpeg的检测方法 |
| CN114636773B (zh) * | 2022-05-23 | 2022-08-23 | 广东国标医药科技有限公司 | 一种药用辅料中聚乙二醇单甲醚2000的含量测定方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101133322A (zh) * | 2005-03-04 | 2008-02-27 | 陶氏环球技术公司 | 分析活化聚乙二醇化合物的方法 |
| US20130096191A1 (en) * | 2010-10-20 | 2013-04-18 | William Wayne Howard | Benzonatate Compositions and Methods of Use |
| CN104927041A (zh) * | 2015-05-25 | 2015-09-23 | 河北科技大学 | 沃尼妙林前药及其制备方法和检测方法 |
| CN112903860A (zh) * | 2021-01-25 | 2021-06-04 | 人福普克药业（武汉）有限公司 | 苯佐那酯中有关物质mpeg的检测方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2015012092A (es) * | 2013-03-13 | 2016-04-06 | Tris Pharma Inc | Capsulas y comprimidos solidos de benzonatato de liberacion modificada. |
| US9180104B2 (en) * | 2013-03-13 | 2015-11-10 | Tris Pharma, Inc. | Benzonatate modified release solid tablets and capsules |
| CN105067727B (zh) * | 2015-09-10 | 2017-06-27 | 四川石达化学股份有限公司 | 一种聚羧酸减水剂大单体中聚乙二醇含量的测定方法 |
| CN105548422B (zh) * | 2015-12-23 | 2018-04-20 | 先健科技(深圳)有限公司 | 一种聚乙二醇含量的检测方法 |
-
2021
- 2021-01-25 CN CN202110098008.6A patent/CN112903860B/zh active Active
- 2021-09-15 WO PCT/CN2021/118400 patent/WO2022156241A1/zh active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101133322A (zh) * | 2005-03-04 | 2008-02-27 | 陶氏环球技术公司 | 分析活化聚乙二醇化合物的方法 |
| US20130096191A1 (en) * | 2010-10-20 | 2013-04-18 | William Wayne Howard | Benzonatate Compositions and Methods of Use |
| CN104927041A (zh) * | 2015-05-25 | 2015-09-23 | 河北科技大学 | 沃尼妙林前药及其制备方法和检测方法 |
| CN112903860A (zh) * | 2021-01-25 | 2021-06-04 | 人福普克药业（武汉）有限公司 | 苯佐那酯中有关物质mpeg的检测方法 |
Non-Patent Citations (1)
| Title |
|---|
| SAFAA M. KISHK, ISMAIL SALAMA, SAMIA MOSTAFA, MOHAMED EL-SADEK: "Stability-Indicating Chromatographic Method for the Determination of Benzonatate, Diphenhydramine, Guaifenesin, and Phenylephrine", JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES, vol. 37, no. 5, 16 March 2014 (2014-03-16), US , pages 726 - 747, XP009538432, ISSN: 1082-6076, DOI: 10.1080/10826076.2012.758140 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112903860B (zh) | 2022-05-27 |
| CN112903860A (zh) | 2021-06-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2022156241A1 (zh) | 苯佐那酯中有关物质mpeg的检测方法 | |
| CN113514584A (zh) | 一种对食品中非法添加的托拉塞米进行定性、定量检测的方法及应用 | |
| CN107315058A (zh) | 一种检测银杏叶提取液中总银杏酸的方法 | |
| CN108020627B (zh) | 一种超高效合相色谱-串联质谱法测定烟草中三种苯氧羧酸类农药残留量的方法 | |
| Ahmed et al. | Stability-indicating TLC-densitometric and HPLC methods for the simultaneous determination of piracetam and vincamine in the presence of their degradation products | |
| CN113702514A (zh) | 一种阿托伐他汀钙有关杂质ⅰ的测定方法 | |
| CN114324642B (zh) | 一种氢溴酸右美沙芬有关物质的测定方法 | |
| CN110007033A (zh) | 同步检测青蒿素、双氢青蒿素、青蒿琥酯含量的方法 | |
| CN108872406B (zh) | 一种门冬氨酸原料药中有关物质的hplc分析检测方法 | |
| CN109632992A (zh) | 一种桃仁配方颗粒中d-苦杏仁苷的含量测定方法 | |
| CN115047093A (zh) | 一种无水咖啡因中硫酸二甲酯检测方法 | |
| CN107884503A (zh) | 蛤蚧定喘丸中22种非法添加止咳平喘类药物的检测方法 | |
| CN107102078A (zh) | 一种测定栀子黄中黄曲霉毒素b1的方法 | |
| CN113820417A (zh) | 一种分离测定吡罗昔康及其杂质的方法 | |
| CN109001342B (zh) | 一种检测n-2,3-二甲氧苄基胡椒乙胺及其盐含量的高效液相方法 | |
| CN111965269A (zh) | 一种超高效液相色谱法测定墓头回中齐墩果酸、熊果酸含量的方法 | |
| CN106053685B (zh) | 一种测定乐舒洗液中黄柏碱含量的spe‑hplc法 | |
| CN111707749B (zh) | 一种气相色谱-质谱法测定中药液体制剂中苯酚的方法 | |
| CN115420830B (zh) | 一种定量检测金贝口服液挥发性成分的gc-ms方法 | |
| CN110045034B (zh) | 一种高效液相色谱测定二芥酰磷脂酰胆碱含量的方法 | |
| CN115166091B (zh) | 一种超高效液相色谱-串联质谱法同时检测食品中5种化学降血压药物的方法 | |
| CN114720614B (zh) | 一种hplc-cad法检测积雪草苷-b和/或羟基积雪草苷含量的方法 | |
| CN113866320B (zh) | 一种用超高效液相色谱检测延胡索生物碱含量的方法 | |
| CN107091895B (zh) | 采用hplc分离测定利奥西呱原料药中有关物质的方法 | |
| CN117538465A (zh) | 一种svhc列表中具有c5-c11直链或支链的邻苯二甲酸酯类化合物的检测方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21920619 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 21920619 Country of ref document: EP Kind code of ref document: A1 |