CN103760245A - HPLC-MS multi-index rapid detection method for illegally added cough and asthma relieving chemical components - Google Patents
HPLC-MS multi-index rapid detection method for illegally added cough and asthma relieving chemical components Download PDFInfo
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Abstract
The invention relates to an HPLC-MS (high performance liquid chromatography-mass spectrometry) multi-index rapid detection method for illegally added cough and asthma relieving chemical components. The key point of the method lies in that the control sample is a mixture of theophylline, sulfamethoxazole, chlorphenamine, diphenhydramine, Pentoxyverine, benproperine, prednisone acetate and diazepam. The invention establishes an efficient detection method for illegally added cough and asthma relieving chemical components. The method has no significant difference from single index detection item, detection limit and specificity, and has very high detection efficiency.
Description
Technical field
The present invention relates to the method for quick of illegal adding ingredient in a kind of health food and medicine, relate in particular liquid-matter multiple index quick detecting method of the relieving cough and asthma class chemical composition of a kind of illegal interpolation.
Technical background
LC-MS-MS (HPLC-MS) is LC-MS technology.The piece-rate system of this technology is liquid chromatography, detection system is mass spectrum, utilize the isolation technics of chromatogram, biased sample is separated into single material, enter in order after mass spectrum, these materials are broken into pieces by mass spectrographic mass analyzer, by mass detector, carried out the structure of amalyzing substances, utilize the fracture mode that judges key, by karyoplasmic ratio, shine corresponding contrast picture library, judge the structure of fragment ion, thereby unknown sample is carried out to qualitative, quantitative.This LC-MS technology has embodied chromatogram and mass spectrographic mutual supplement with each other's advantages, chromatogram and mass spectrographic advantages are got up, allow people in analysis, can utilize the features such as their high separating force, high sensitivity and high selectivity, the system of adding can provide contrast spectrogram, makes the analytical test can more and more easier circle.LC-MS is the technology of comparative maturity, in current many fields as the aspects such as pesticide residue analysis, food analysis, environmental analysis and Pharmaceutical Analysis are widely used.LC-MS system conventional on present analysis is divided into mass analyzer classification and ion gun classification two large classes from mass spectrum direction substantially.Mass analyzer classification comprises level Four bar, flight time (TOF), Fourier transform mass spectrum: ion gun classification comprises Atmosphere Pressure Chemical Ionization (APCI) source (APCI), atmospheric pressure photoionization source (APPI), electric spray ion source (ESI), substance assistant laser desorpted ionized source (MALDI).
Detecting device with traditional liquid chromatography, as UV or PAD comparison, mass spectrum has highly sensitive and identifies the features such as function is strong, adds that the analyst coverage of liquid chromatography is wider, and LC-MS technology has become one of the most strong instrument of big event Chinese traditional medicine analysis aspect in recent years.Especially in recent years for the research of various medicines especially forbidden drug and metabolic product thereof, there is a large amount of bibliographical informations both at home and abroad.
Summary of the invention
But due to very many for a certain medicine or the addible similar chemical composition of health products, as detected one by one for each composition, not only testing cost is huge, needs a large amount of detection times simultaneously, is unfavorable for increasing work efficiency; Therefore the invention provides liquid-matter multiple index quick detecting method of the relieving cough and asthma class chemical composition of a kind of illegal interpolation.Concrete operation steps is:
1) get the Chinese patent drug or the health food (solid pharmaceutical preparation needs porphyrize, liquid preparation direct sample) that are equivalent to an oral dose, add methyl alcohol 25ml, ultrasonic processing 10 minutes, with miillpore filter (0.45um) filtration, filtrate is suitably diluted with methyl alcohol, as need testing solution.
2) get theophylline, Sulfamethoxazole, chlorphenamine, diphenhydramine, pentoxyverine, benproperine, prednisone acetate, diazepam reference substance appropriate, add respectively methyl alcohol and make the solution of every 1ml containing 0.1mg, product solution in contrast.
3) upper machine testing: sample is carried out to examination and evaluation by high performance liquid chromatography-flight time mass spectrum method for combined use.
High performance liquid chromatograph: waters AQUITY UPLC instrument;
Take octadecylsilane chemically bonded silica as filling agent, (chromatographic column is WATERS BEH C
18, 100mm × 2.1mm, 1.7 μ are m);
Take containing the methyl alcohol of 0.1% formic acid as mobile phase A, take the ammonium formate solution of the 10mmol/L containing 0.1% formic acid as Mobile phase B, according to the form below 1 is to carry out gradient elution;
Table 1HPLC gradient elution mobile phase
Flow velocity: 0.3ml/min;
Column temperature: 40 ℃; ;
Sample temperature: 15 ℃;
Sample size: 1ul;
Time of-flight mass spectrometer: waters Q-TOF instrument;
Electron spray ionisation component (ESI);
The MS detection parameters: ESI+ scanning;
Dry gas temperature: 350 ℃;
Taper hole voltage: 35v;
Scan mode: one-level mass spectrum full scan, second order ms full scan, sweep limit: 100～1000m/z;
4) identify:
In test sample chromatogram, occur and the identical chromatographic peak of each reference substance chromatographic retention in mixing reference substance, and the one-level mass spectrum of this chromatographic peak LC-MS of test sample and second order ms all consistent with reference substance, judge that this test sample is positive.
In test sample chromatogram, there is not the chromatographic peak identical with each reference substance chromatographic retention in mixing reference substance, judge that this test sample is negative.
Useful technique effect of the present invention is: the present invention has set up a kind of relieving cough and asthma class chemical composition of illegal interpolation, efficient detection method, with single index test item, detectability and specificity are all without significant difference; And there is very high detection efficiency.
Accompanying drawing explanation
Fig. 1 reference substance extracts ion current chromatogram;
Fig. 2 reference substance one-level mass spectrogram;
Fig. 3 reference substance second order ms figure;
Fig. 4 negative sample (not detecting chlorphenamine) total ion current figure;
Fig. 5 positive (detecting chlorphenamine) total ion current figure;
Fig. 6 positive (having detected chlorphenamine) is extracted ion flow graph (275.132,0.02Da);
Fig. 7 positive (detecting chlorphenamine) one-level mass spectrogram;
Fig. 8 positive (detecting chlorphenamine) second order ms figure;
Wherein, described in Fig. 1-3, the corresponding chemical composition of numbering is: 1-theophylline, 2-Sulfamethoxazole, 3-chlorphenamine, 4-diphenhydramine, 5-spray Trotskyite woods, 6-benproperine, 7-prednisone acetate, 8-diazepam.
Embodiment
The investigation of embodiment 1 chromatographic condition
1) selection of test sample extraction conditions
Investigated respectively the illegal positive of adding of two kinds of solvent extraction parts of methyl alcohol and acetonitrile, result shows, methyl alcohol and acetonitrile all can extract target component, but because methyl alcohol is cheap and less pollution, therefore adopt the method for the ultrasonic extraction of methyl alcohol.Investigated respectively Strata-X, Strata-X-W, HLB and tetra-kinds of solid phase extraction columns of PCX purification effect to methyl alcohol extraction sample, result all has stronger adsorption effect to target component, causes the recovery low, therefore do not adopt the step of Solid-Phase Extraction.
2) selection of mobile phase
Adopt the chromatographic condition in summary of the invention, water has been investigated respectively formic acid, formic acid-triethylamine, formic acid-ammonium formate, formic acid ammonium formate-triethylamine system, result only adopts formate ion efficiency lower, add the system peak type of triethylamine better, but ion depression effect is obvious, add ammonium formate after Ionization Efficiency obviously strengthen, and peak type is better.Therefore adopt formic acid-ammonium formate system.Organic phase has compared respectively methyl alcohol, acetonitrile, different proportion methyl alcohol-acetonitrile mixed solution, and result adopts methyl alcohol-acetonitrile mixed solution peak type symmetry, sharp-pointed.Repeatedly gradient is adjusted, finally obtained good separating effect.(see figure 1)
3) investigation of different chromatographic column chromatographic resolution situations
Separation case (1) the Agilent ZORBAX RRHD Eclipse Plus C of the chromatographic column of simultaneously having investigated three different brands to composition to be measured
18post (100mm × 3.0mm, 1.8 μ m), (2) Kromasil C
18(100mm × 2.1mm, 1.8 μ m), (3) Waters ACQUITY HSS T3C
18post (100mm × 2.1mm, 1.8 μ m), (4) Waters ACQUITY BEH C
18(100mm × 2.1mm, 1.7 μ m) the bright target component chromatographic peak of test card peak shape are better for post.
4) specificity is investigated
Ingredient in some positive sample has been carried out to specificity investigation, with containing the corresponding formulation of additive and kind as negative control, result shows, positive can detect the chromatographic peak that retention time is identical, negative sample is all without chromatographic peak accordingly; Specifically as shown in Figure 2.
5) detectability test
Get in above-mentioned 11 reference substance appropriate, add methyl alcohol and be mixed with the reference substance solution injection liquid chromatography of variable concentrations, measure in accordance with the law, by 3 times of snr computation detectabilities, the lowest detectable limit of 11 kinds of reference substances is all lower than 0.01 μ gmL
-1.
6) mass spectral characteristic is determined
The one-level mass spectrum molecular ion peak of reference substance and the illegal interpolation of part sample thereof and the main fragmention of second order ms are as shown in Table 2 and Figure 3.
Table 28 kind of the illegal mass spectrum quasi-molecular ions adding
The detection of embodiment 2 samples
Get commercially available certain health food that is equivalent to an oral dose, porphyrize, liquid preparation direct sample, add after the ultrasonic extraction of methyl alcohol, put 10 ℃ of following temperature placements and spend the night, after clarifying, get miillpore filter for supernatant (0.22um) and filter, suitably dilution, as need testing solution.
Adopt the LC-MS described in embodiment preferred, by high performance liquid chromatography-flight time mass spectrum method for combined use, sample is carried out to examination and evaluation.Find this sample and contain illegal interpolation chlorphenamine.Specifically as shown in Fig. 4,5,6,7,8.
Claims (3)
1. the illegal liquid-matter multiple index quick detecting method that adds relieving cough and asthma class chemical composition, comprises the following steps:
1) prepare sample;
2) by high performance liquid chromatography-flight time mass spectrum method for combined use, sample is carried out to examination and evaluation;
3) high-efficient liquid phase chromatogram of the high-efficient liquid phase chromatogram of sample and a second order ms figure and reference substance and a second order ms figure are compared, identify the relieving cough and asthma class chemical composition of illegal interpolation;
It is characterized in that: described reference substance is the potpourri of theophylline, Sulfamethoxazole, chlorphenamine, diphenhydramine, pentoxyverine, benproperine, prednisone acetate and diazepam.
2. liquid-matter multiple index quick detecting method of the relieving cough and asthma class chemical composition of illegal interpolation according to claim 1, is characterized in that:
Step 2) described chromatographic condition is:
High performance liquid chromatograph: waters AQUITY UPLC instrument;
Chromatographic column: take octadecylsilane chemically bonded silica as filling agent, 100 mm × 2.1 mm, 1.7 μ m;
Take containing the methyl alcohol of 0.1% formic acid as mobile phase A, take the ammonium formate solution of the 10mmol/L containing 0.1% formic acid as Mobile phase B, according to the form below is to carry out gradient elution;
During 0-6min, the percent by volume of mobile phase A is changed to 30% → 80%, and Mobile phase B percent by volume is changed to 70% → 20%;
During 6-7min, the percent by volume of mobile phase A is 80%, and Mobile phase B percent by volume is 20%;
During 7-8min, the percent by volume of mobile phase A is changed to 80% → 30%, and Mobile phase B percent by volume is changed to 20% → 70%;
During 8-10min, the percent by volume of mobile phase A is 30%, and Mobile phase B percent by volume is 70%;
Flow velocity: 0.3ml/min;
Column temperature: 40 ℃;
Sample temperature: 15 ℃;
Sample size: 1ul;
Time of-flight mass spectrometer: waters Q-TOF instrument;
Electron spray ionisation component (ESI);
The MS detection parameters: ESI
+scanning;
Dry gas temperature: 350 ℃;
Taper hole voltage: 35v;
Scan mode: one-level mass spectrum full scan, second order ms full scan, sweep limit: 100～1000 m/z.
3. liquid-matter multiple index quick detecting method of the relieving cough and asthma class chemical composition of illegal interpolation according to claim 1, is characterized in that:
Described in step 1), for examination preparation method, be: get and be equivalent to the Chinese patent drug of an oral dose or health food (solid pharmaceutical preparation needs porphyrize, liquid preparation direct sample), add methyl alcohol 25ml, ultrasonic processing 10 minutes, filter with miillpore filter (0.45um), filtrate is suitably diluted with methyl alcohol, as need testing solution.
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104833757A (en) * | 2015-05-12 | 2015-08-12 | 广西壮族自治区梧州食品药品检验所 | Method of simultaneously determining multiple chemical drugs illegally added in soft capsule health food |
| CN104931601A (en) * | 2015-05-12 | 2015-09-23 | 广西壮族自治区梧州食品药品检验所 | Method for simultaneously detecting multiple chemical medicines illegally added into liquid health-care food |
| CN105158358A (en) * | 2015-08-18 | 2015-12-16 | 江苏出入境检验检疫局动植物与食品检测中心 | Method for detecting illegally-added 42 chemicals in Chinese patent medicines and health care products simultaneously |
| CN107677743A (en) * | 2017-09-28 | 2018-02-09 | 广东省药品检验所（广东省药品质量研究所、广东省口岸药品检验所） | A kind of method of chlorphenamine maleate and other chemicalses in detection herbal beverage |
| CN107741465A (en) * | 2017-11-27 | 2018-02-27 | 浙江公正检验中心有限公司 | The detection method of 18 kinds of illegal addition hypoglycemic antihypertensive drugs residual quantities in health products |
| CN107884503A (en) * | 2017-11-01 | 2018-04-06 | 广西壮族自治区食品药品检验所 | 22 kinds of detection methods for illegally adding relieving cough and asthma class medicine in asthma-relieving bolus of gecko |
| CN108051534A (en) * | 2017-11-20 | 2018-05-18 | 中山大学 | A kind of method of the 132 kinds of chemicalses illegally added in rapid screening Chinese patent drug and health products |
| CN113791162A (en) * | 2021-11-16 | 2021-12-14 | 潍坊市检验检测中心 | Method for determining 35 chemical components illegally added in patch for relieving cough and asthma of children |
| CN117214125A (en) * | 2023-11-09 | 2023-12-12 | 南京盛略科技有限公司 | Liquid component detection system and method based on detection optical fiber |
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104833757A (en) * | 2015-05-12 | 2015-08-12 | 广西壮族自治区梧州食品药品检验所 | Method of simultaneously determining multiple chemical drugs illegally added in soft capsule health food |
| CN104931601A (en) * | 2015-05-12 | 2015-09-23 | 广西壮族自治区梧州食品药品检验所 | Method for simultaneously detecting multiple chemical medicines illegally added into liquid health-care food |
| CN105158358A (en) * | 2015-08-18 | 2015-12-16 | 江苏出入境检验检疫局动植物与食品检测中心 | Method for detecting illegally-added 42 chemicals in Chinese patent medicines and health care products simultaneously |
| CN107677743A (en) * | 2017-09-28 | 2018-02-09 | 广东省药品检验所（广东省药品质量研究所、广东省口岸药品检验所） | A kind of method of chlorphenamine maleate and other chemicalses in detection herbal beverage |
| CN107884503A (en) * | 2017-11-01 | 2018-04-06 | 广西壮族自治区食品药品检验所 | 22 kinds of detection methods for illegally adding relieving cough and asthma class medicine in asthma-relieving bolus of gecko |
| CN108051534A (en) * | 2017-11-20 | 2018-05-18 | 中山大学 | A kind of method of the 132 kinds of chemicalses illegally added in rapid screening Chinese patent drug and health products |
| CN108051534B (en) * | 2017-11-20 | 2019-10-18 | 中山大学 | A kind of method of the 132 kinds of chemicals illegally added in rapid screening Chinese patent drug and health care product |
| CN107741465A (en) * | 2017-11-27 | 2018-02-27 | 浙江公正检验中心有限公司 | The detection method of 18 kinds of illegal addition hypoglycemic antihypertensive drugs residual quantities in health products |
| CN107741465B (en) * | 2017-11-27 | 2020-12-04 | 浙江公正检验中心有限公司 | Method for detecting residual quantity of 18 illegally added hypoglycemic and antihypertensive drugs in health care product |
| CN113791162A (en) * | 2021-11-16 | 2021-12-14 | 潍坊市检验检测中心 | Method for determining 35 chemical components illegally added in patch for relieving cough and asthma of children |
| CN117214125A (en) * | 2023-11-09 | 2023-12-12 | 南京盛略科技有限公司 | Liquid component detection system and method based on detection optical fiber |
| CN117214125B (en) * | 2023-11-09 | 2024-01-26 | 南京盛略科技有限公司 | Liquid component detection system and method based on detection optical fiber |
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