CN115494174B - Method for detecting thiourea in meloxicam by high performance liquid chromatography - Google Patents
Method for detecting thiourea in meloxicam by high performance liquid chromatography Download PDFInfo
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- CN115494174B CN115494174B CN202211166654.2A CN202211166654A CN115494174B CN 115494174 B CN115494174 B CN 115494174B CN 202211166654 A CN202211166654 A CN 202211166654A CN 115494174 B CN115494174 B CN 115494174B
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- thiourea
- meloxicam
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- liquid chromatography
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- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 title claims abstract description 91
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title claims abstract description 45
- 238000000034 method Methods 0.000 title claims abstract description 33
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 229960001929 meloxicam Drugs 0.000 title claims abstract description 29
- 238000004128 high performance liquid chromatography Methods 0.000 title claims abstract description 12
- 238000001514 detection method Methods 0.000 claims abstract description 17
- PUUZLWLFYQFYCF-UHFFFAOYSA-N n-ethylethanamine;hexane;propan-2-ol Chemical compound CC(C)O.CCNCC.CCCCCC PUUZLWLFYQFYCF-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000000243 solution Substances 0.000 claims description 24
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- 238000012360 testing method Methods 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 6
- 239000013558 reference substance Substances 0.000 claims description 5
- 238000007865 diluting Methods 0.000 claims description 4
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 3
- 238000010812 external standard method Methods 0.000 claims description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 2
- 239000012085 test solution Substances 0.000 claims description 2
- 238000011084 recovery Methods 0.000 abstract description 6
- 230000035945 sensitivity Effects 0.000 abstract description 6
- 238000000926 separation method Methods 0.000 abstract description 5
- 238000003908 quality control method Methods 0.000 abstract description 2
- KZCXMZLEEWLBFE-UHFFFAOYSA-N (3-chloro-4-methylphenyl) carbamate Chemical compound CC1=CC=C(OC(N)=O)C=C1Cl KZCXMZLEEWLBFE-UHFFFAOYSA-N 0.000 abstract 1
- 239000000945 filler Substances 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 4
- 239000012488 sample solution Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 2
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 231100000357 carcinogen Toxicity 0.000 description 2
- 239000003183 carcinogenic agent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 229920000298 Cellophane Polymers 0.000 description 1
- 108010037464 Cyclooxygenase 1 Proteins 0.000 description 1
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000004305 normal phase HPLC Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- 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
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/027—Liquid chromatography
Abstract
The invention relates to a method for detecting thiourea in meloxicam by high performance liquid chromatography, which takes amylose-tri (3-chloro-4-methylphenyl carbamate) as a filler; diethylamine-n-hexane-isopropanol is used as a mobile phase, and the proportion of the diethylamine-n-hexane-isopropanol is 0.1:30-35:70-65; the flow rate is 0.4 mL/min-0.6 mL/min; the column temperature is 25-35 ℃; the detection wavelength is 238 nm-242 nm; the high performance liquid chromatography provided by the invention is used for detecting thiourea in meloxicam, the separation degree of the thiourea and meloxicam is good, the sensitivity of the thiourea is high, the repeatability is good, the recovery rate is between 85% and 110%, and the method has good durability and can be used for quality control of meloxicam.
Description
Technical Field
The invention belongs to the field of medicine analysis, and particularly relates to a method for detecting thiourea in meloxicam by using a high performance liquid chromatography.
Background
Meloxicam (Meloxicam), an enol non-steroidal anti-inflammatory drug, has anti-inflammatory, analgesic and antipyretic effects, and can selectively inhibit cyclooxygenase-2 (COX-2), and has weak inhibition effect on cyclooxygenase-1, so that adverse effects such as digestive system are less. The chemical structural formula is shown as formula (I), and the molecular formula is as follows: c (C) 14 H 13 N 3 O 4 S 2 Molecular weight: 351.40, CAS number: 71125-38-7.
Thiourea is an impurity introduced in meloxicam production, and a carcinogen list published by the international cancer research institute of world health organization is primarily arranged and referenced, belongs to 3 types of carcinogens, and is controlled according to the limit of 1.5 mug/day specified by the toxicological attention threshold (TTC) of ICH, and the limit is lower. The chemical structural formula is shown as a formula (II), and the molecular formula is as follows: CH (CH) 4 N 2 S, molecular weight: 76.12, cas number: 62-56-6.
As reported in literature, the existing thiourea detection methods include an LC-MS/MS method, a reversed phase HPLC method and the like. The LC-MS/MS method has the advantages of expensive instrument and low popularity; the sensitivity of the reverse phase HPLC method does not meet the existing requirements. By combining the characteristics of the product and thiourea, a normal-phase HPLC method is developed, and the method has the advantages of good specificity, high sensitivity, high accuracy and good durability.
Disclosure of Invention
The invention provides a method for detecting thiourea in meloxicam by high performance liquid chromatography, which is characterized by comprising the following steps of:
1) Chromatographic conditions: CHIRALPAK IF-34.6mm×250mm is used as chromatographic column; diethylamine-n-hexane-isopropanol is used as a mobile phase, and the proportion of the diethylamine-n-hexane-isopropanol is 0.1:30-35:70-65; the flow rate of the mobile phase is 0.4 mL/min-0.6 mL/min; the column temperature is 25-35 ℃; the detection wavelength is 238 nm-242 nm;
2) Preparing thiourea reference substance solution: taking thiourea reference substance, and dissolving and diluting with mobile phase;
3) Preparing a test solution: taking meloxicam, dissolving and diluting with a mobile phase;
4) And (3) measuring: and precisely measuring 20 mu l of each of the thiourea reference substance solution and the test substance solution, injecting into a liquid chromatograph, recording the chromatograms, and calculating the thiourea content in the test substance solution according to an external standard method by using the peak area.
The high performance liquid chromatography provided by the invention detects thiourea in meloxicam, the thiourea peak and the peripheral chromatographic peak reach baseline separation, the quantitative limit of the thiourea reaches 0.06 mug/ml, the sensitivity is high, the repeatability is good, the recovery rate is between 85% and 110%, the method has good durability, and the method can be used for quality control of meloxicam.
Drawings
Fig. 1 shows the method specific experiment of example 1—blank solvent.
Fig. 2 shows the method specific experiments of example 1-thiourea localization solution.
Figure 3 shows the procedure specific experiments of example 1-meloxicam solution.
FIG. 4 shows the method specific experiments of example 1-100% spiked sample solutions.
Detailed Description
Example 1: method specificity
Preparation of mobile phase:
measuring 1mL of diethylamine, 300mL of normal hexane and 700mL of isopropanol, uniformly mixing, filtering by using a microporous filter membrane with the thickness of 0.45 mu m, and performing ultrasonic degassing to obtain the product.
Solution preparation:
preparing thiourea positioning solution: a proper amount of thiourea was taken, dissolved and diluted with a mobile phase to prepare a solution containing about 0.2. Mu.g of thiourea per 1 mL.
Meloxicam solution preparation: a suitable amount of meloxicam was taken, dissolved in the mobile phase and diluted to a solution containing approximately 2mg meloxicam per 1 mL.
Preparing 100% standard sample solution: the meloxicam and thiourea are dissolved in mobile phase and diluted to prepare solution of meloxicam 2mg and thiourea 0.2 mug in 1 mL.
The chromatographic conditions were as follows:
chromatographic column: cellophane CHIRALPAK IF-34.6mm×250mm;
mobile phase: diethylamine-n-hexane-isopropanol (0.1:30:70);
flow rate: 0.5mL/min; column temperature: 30 ℃; detection wavelength: 240nm; sample injection volume: 20 μl; run time: and 40min.
Results: the blank has no interference. The retention time of thiourea is 7.097min, the retention time of meloxicam is 15.257min, the separation degree of thiourea and meloxicam is 5.7 and is more than 1.5, and the method can realize complete separation of thiourea and meloxicam and has good specificity.
Example 2: quantitative limit and detection limit of method
Preparing quantitative limiting solution: a suitable amount of thiourea was taken, dissolved and diluted with the mobile phase to give a solution of about 0.06. Mu.g of thiourea per 1 mL.
Preparing a detection limit solution: a suitable amount of thiourea was taken, dissolved and diluted with the mobile phase to give a solution of about 0.02. Mu.g of thiourea per 1 mL.
The quantitative limiting solution 20. Mu.l was measured precisely and continuously fed 6 times, and the detection limiting solution 20. Mu.l was fed 1 time, and the results are shown in Table 1 below:
TABLE 1 quantitative limit and detection limit experiment results
| Sample of | Retention time min | Peak area | Signal to noise ratio |
| Quantitative limit-1 | 7.100 | 0.2641 | 93.0 |
| Quantitative limit-2 | 7.083 | 0.2537 | 145.8 |
| Quantitative limit-3 | 7.088 | 0.2699 | 160.3 |
| Quantitative limit-4 | 7.082 | 0.2382 | 156.8 |
| Limit of quantification-5 | 7.077 | 0.2388 | 115.9 |
| Limit of quantification-6 | 7.072 | 0.2261 | 102.3 |
| Average value of | 7.084 | 0.2485 | / |
| RSD | 0.2％ | 6.9％ | / |
| Detection limit | 7.088 | 0.0991 | 26.3 |
The quantitative limiting solution is continuously injected for 6 times, the retention time RSD of thiourea peak is less than or equal to 1.0%, the peak area RSD is less than or equal to 10%, and the signal to noise ratio is 93.0 at minimum; in the detection limiting solution, the signal to noise ratio of the thiourea peak is more than 3; the sensitivity of the method can meet the detection requirement of thiourea, and the method has high sensitivity.
Example 3: method accuracy and repeatability experiments
6 100% standard sample solutions were prepared in parallel for analysis and detection, and the recovery rate was calculated as peak area according to the external standard method, and the results are shown in Table 2 below:
TABLE 2 recovery test results
| Sample of | 1 | 2 | 3 | 4 | 5 | 6 | Average value of | RSD |
| Recovery rate | 89.52％ | 89.58％ | 88.98％ | 88.45％ | 88.35％ | 88.53％ | 88.90％ | 0.7％ |
The recovery rate of 100% of the standard sample solution is between 85 and 110%, and RSD is less than or equal to 4.0%; the accuracy and the repeatability of the method meet the detection requirement of thiourea, and the method has high accuracy and good repeatability.
Example 4: durability test
By adjusting the flow rate, mobile phase ratio, column temperature, and wavelength of the chromatographic conditions, the degree to which the measurement results were not affected was examined, and the results are shown in table 3 below:
TABLE 3 durability test results
Under each durability condition, the separation degree of thiourea and meloxicam meets the requirement, and the difference between the measured value of the thiourea and the original condition is 0.001% at maximum; the method has basically consistent detection results of thiourea in the detection wavelength of 238-242 nm, the flow rate of 0.4-0.6 ml/min, the column temperature of 25-35 ℃ and the isopropanol proportion of 65-70%, and shows that the method has good durability.
Claims (5)
1. A method for detecting thiourea in meloxicam by high performance liquid chromatography is characterized in that:
1) Chromatographic conditions: CHIRALPAK IF-34.6mm×250mm is used as chromatographic column; diethylamine-n-hexane-isopropanol is used as a mobile phase, and the proportion of the diethylamine-n-hexane-isopropanol is 0.1:30-35:70-65; the flow rate of the mobile phase is 0.4 mL/min-0.6 mL/min; the column temperature is 25-35 ℃; the detection wavelength is 238 nm-242 nm;
2) Preparing thiourea reference substance solution: dissolving and diluting with mobile phase;
3) Preparing a test solution: dissolving and diluting with mobile phase;
4) And (3) measuring: and precisely measuring 20 mu l of each of the thiourea reference substance solution and the test substance solution, injecting into a liquid chromatograph, recording the chromatograms, and calculating the thiourea content in the test substance solution according to an external standard method by using the peak area.
2. The method for detecting thiourea in meloxicam by high performance liquid chromatography according to claim 1, wherein: the ratio of the mobile phase diethylamine to the normal hexane to the isopropanol is 0.1:30:70.
3. The method for detecting thiourea in meloxicam by high performance liquid chromatography according to claim 1, wherein: the ratio of the mobile phase diethylamine to the normal hexane to the isopropanol is 0.1:35:65.
4. The method for detecting thiourea in meloxicam by high performance liquid chromatography according to claim 1, wherein: the mobile phase flow rate was 0.5ml/min.
5. The method for detecting thiourea in meloxicam by high performance liquid chromatography according to claim 1, wherein: the detection wavelength is 240nm.
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008151757A (en) * | 2006-12-20 | 2008-07-03 | Mitsui Mining & Smelting Co Ltd | Quantitative determination method for thiourea |
| CN103698436A (en) * | 2013-12-30 | 2014-04-02 | 四川科伦药业股份有限公司 | Method for detecting enantiomer in pramipexole dihydrochloride and method for separating enantiomer from pramipexole dihydrochloride |
| CN104133012A (en) * | 2014-07-02 | 2014-11-05 | 北京万全德众医药生物技术有限公司 | Method for determining asenapine maleate racemate by using HPLC |
| CN105675733A (en) * | 2014-11-17 | 2016-06-15 | 重庆医药工业研究院有限责任公司 | Method for using liquid chromatography method for separation and determination of trelagliptin succinate and trelagliptin succinate optical isomers |
| CN106896162A (en) * | 2015-12-17 | 2017-06-27 | 瑞普（天津）生物药业有限公司 | A kind of HPLC methods of impurity in detection meloxicam tablet |
| CN107192766A (en) * | 2016-03-14 | 2017-09-22 | 广东东阳光药业有限公司 | A kind of method that Su Woleisheng chiral isomers are determined with HPLC |
| CN109206349A (en) * | 2017-11-17 | 2019-01-15 | 西陇科学股份有限公司 | A kind of production method of high-purity thiourea |
| CN111983075A (en) * | 2020-08-17 | 2020-11-24 | 重庆华森制药股份有限公司 | Method for detecting rasagiline and enantiomer thereof |
| KR20220108872A (en) * | 2021-01-27 | 2022-08-04 | 대화제약 주식회사 | Method for qualitative or quantitative analysis of nitrosamines and quality control method of medicines usinig the same |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003243055A1 (en) * | 2003-07-10 | 2005-01-28 | Arturo Jimenez Bayardo | Method of preparing an aqueous meloxicam solution and aqueous solution thus produced |
-
2022
- 2022-09-23 CN CN202211166654.2A patent/CN115494174B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008151757A (en) * | 2006-12-20 | 2008-07-03 | Mitsui Mining & Smelting Co Ltd | Quantitative determination method for thiourea |
| CN103698436A (en) * | 2013-12-30 | 2014-04-02 | 四川科伦药业股份有限公司 | Method for detecting enantiomer in pramipexole dihydrochloride and method for separating enantiomer from pramipexole dihydrochloride |
| CN104133012A (en) * | 2014-07-02 | 2014-11-05 | 北京万全德众医药生物技术有限公司 | Method for determining asenapine maleate racemate by using HPLC |
| CN105675733A (en) * | 2014-11-17 | 2016-06-15 | 重庆医药工业研究院有限责任公司 | Method for using liquid chromatography method for separation and determination of trelagliptin succinate and trelagliptin succinate optical isomers |
| CN106896162A (en) * | 2015-12-17 | 2017-06-27 | 瑞普（天津）生物药业有限公司 | A kind of HPLC methods of impurity in detection meloxicam tablet |
| CN107192766A (en) * | 2016-03-14 | 2017-09-22 | 广东东阳光药业有限公司 | A kind of method that Su Woleisheng chiral isomers are determined with HPLC |
| CN109206349A (en) * | 2017-11-17 | 2019-01-15 | 西陇科学股份有限公司 | A kind of production method of high-purity thiourea |
| CN111983075A (en) * | 2020-08-17 | 2020-11-24 | 重庆华森制药股份有限公司 | Method for detecting rasagiline and enantiomer thereof |
| KR20220108872A (en) * | 2021-01-27 | 2022-08-04 | 대화제약 주식회사 | Method for qualitative or quantitative analysis of nitrosamines and quality control method of medicines usinig the same |
Non-Patent Citations (7)
| Title |
|---|
| 2-氨基-5-甲基噻唑合成工艺的改进;张治国, 张奕华, 李雅静;中国药物化学杂志(第01期);全文 * |
| E.M. Malone,等.Development of a rapid, multi-class method for the confirmatory analysis of anti-inflammatory drugs in bovine milk using liquid chromatography tandem mass spectrometry.Journal of Chromatography A.2009,第1216卷全文. * |
| 亲水作用色谱法测定食品及烟用香料中的硫脲;汤威;赵瑜;杨华武;陈波;;中国卫生检验杂志(第07期);全文 * |
| 基质分散固相萃取-高效液相色谱-串联质谱法快速测定婴幼儿配方乳粉中19种非蛋白氮化合物;赵善贞;伊雄海;程甲;潘孝博;郭德华;朱坚;邓晓军;;分析化学(第08期);全文 * |
| 美洛昔康原药中有关物质和降解产物的HPLC测定;胡欣, 曹国颖, 宋友华;中国医药工业杂志(第03期);全文 * |
| 通过式固相萃取 - 高效液相色谱法测定小麦粉及面粉处理剂中的硫脲;丁一，等;中国食品卫生杂志;第34卷(第4期);第751页 * |
| 高效液相色谱法测定人血浆中美洛昔康的浓度;熊海燕;谢凤云;;中国现代医药杂志(第06期);全文 * |
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