CN117665174B - Method for detecting PDE5 and SSRI and application thereof - Google Patents
Method for detecting PDE5 and SSRI and application thereof Download PDFInfo
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Abstract
The application discloses a method for detecting PDE5 and SSRI and application thereof, and relates to the technical field of instrument analysis. A method of detecting PDE5 and SSRI, the steps of which include sample processing and instrumental analysis; the method is applied to foods, health-care products and Chinese patent medicines, and can detect and analyze PDE5 and SSRI inhibitor substances contained in a sample, so as to judge whether the product is illegally added with the compounds or not, thereby guaranteeing the rights and interests of consumers; the detection method is simple, low in cost, good in separation efficiency, accurate in quantification, good in repeatability and strong in specificity, and has extremely high application value.
Description
Technical Field
The application relates to the technical field of instrument analysis, in particular to a method for detecting PDE5 and SSRI and application thereof.
Background
The traditional Chinese patent medicines and health care products with the effects of tonifying kidney and strengthening yang in the current market are various, and some of the foods, the traditional Chinese patent medicines and the health care products may be added with some chemical medicines for tonifying kidney and strengthening yang. Because of the uncertainty of the types and the additive amounts of the added chemical medicaments, consumers can take the chemical medicaments for a long time or excessively without knowing, and a plurality of adverse reactions can be caused, so that great potential safety hazards are brought to the health of the consumers.
At present, the ingredients of the detection substances aiming at tonifying kidney and strengthening yang mainly comprise a type 5 phosphodiesterase (PDE 5) inhibitor and derivatives thereof. The 5-hydroxytryptamine reuptake inhibitor (SSRI) for treating male premature ejaculation, such as dapoxetine hydrochloride, fluoxetine hydrochloride, sertraline hydrochloride and the like, has the characteristics of quick response and definite curative effect, and can also become another trend of illegal addition in kidney-tonifying yang-strengthening foods, health care products and Chinese patent medicines.
The current test methods of foods, health foods or Chinese patent medicines have few reports related to SSRI medicines, and lack of test methods related to PDE5 and more than two SSRI at the same time. At the same time, in the existing detection methods for illegally adding chemical substances in foods, health care products and Chinese patent medicines, mass spectrometry is mostly adopted, but the instruments involved in the method are expensive, the detection cost is high, and the popularization of basic level inspection is not easy.
Disclosure of Invention
The application aims to provide a method for detecting PDE5 and SSRI, which can effectively detect PDE5 and SSRI substances contained in a sample, has good detection and separation efficiency, accurate quantification and good repeatability, and is beneficial to popularization and application.
The application also aims to provide application of the method for detecting PDE5 and SSRI in detecting foods, health products or Chinese patent medicines, which can effectively detect and analyze PDE5 and SSRI added in kidney-tonifying and yang-strengthening foods, health products and Chinese patent medicines.
The technical scheme of the application is as follows:
in one aspect, embodiments of the present application provide a method of detecting PDE5 and SSRI, comprising the steps of:
sample treatment: taking a sample to be tested, adding acetonitrile, performing ultrasonic treatment, cooling to room temperature, performing centrifugal treatment, and taking supernatant to filter to obtain a sample solution to be tested;
instrument analysis: detecting the sample solution to be tested by using HPLC-PDA equipment, and detecting PDE5 and SSRI inhibitor substances contained in the sample;
in the sample processing step, the sample to be detected is a liquid sample or a fixed sample;
when the sample to be measured is a liquid sample: placing 10ml of liquid sample into a 50ml volumetric flask, adding 30ml of acetonitrile, performing ultrasonic treatment, cooling to room temperature, then fixing the volume to 50ml, performing centrifugal treatment, and taking supernatant to filter to obtain a sample solution to be tested;
When the sample to be detected is a solid sample, grinding and crushing the solid sample, taking the crushed solid sample which is equal to the once oral dosage of the sample, placing the solid sample into a 50ml volumetric flask, adding 30ml acetonitrile, performing ultrasonic treatment, cooling to room temperature, then fixing the volume to 50ml, performing centrifugal treatment, and taking supernatant to filter to obtain the solution of the sample to be detected.
Further, in some embodiments of the present application, in the sample processing step, the ultrasonic treatment is performed at a power of 300W and a frequency of 40kHz for 15 minutes; centrifuging at 20deg.C at 7000r/min for 5min; the supernatant was filtered through a 0.22 μm microporous organic filter.
Further, in some embodiments of the present application, in the above instrument analysis step, the SSRI species are dapoxetine hydrochloride, fluoxetine hydrochloride, and sertraline hydrochloride, and the PDE5 species are nadir, erythronafil, thioidenafil, sildenafil, deluxifen, namxidenafil, amino tadalafil, hydroxydeluxifen citrate, vardenafil, and pseudo vardenafil.
Further, in some embodiments of the present application, in the step of analyzing the apparatus, the liquid chromatography conditions are: adopting a C 18 column with the specification of 250 multiplied by 4.6mm and 5 mu m as a chromatographic column; mobile phase A is acetonitrile, mobile phase B is 10mmol/L ammonium acetate aqueous solution containing 0.1% triethylamine; the column temperature is 30-35 ℃, the sample injection volume is 5-10 mu L, and the flow rate is as follows: gradient elution was carried out for 65min at 1.0 mL/min.
Further, in some embodiments of the present application, in the step of analyzing the apparatus, the gradient elution procedure is as follows:
0-8 min, the ratio of the mobile phase A is increased from 10% to 30%, and the ratio of the mobile phase B is decreased from 90% to 70%;
8-16 min, the ratio of the mobile phase A is increased from 30% to 37%, and the ratio of the mobile phase B is decreased from 70% to 63%;
16-23 min, the ratio of the mobile phase A is kept 37%, and the ratio of the mobile phase B is kept 63%;
23-23.1 min, the ratio of the mobile phase A is increased from 37% to 41%, and the ratio of the mobile phase B is decreased from 63% to 59%;
23.1-28 min, the ratio of the mobile phase A is kept 41%, and the ratio of the mobile phase B is kept 59%;
28-50 min, the ratio of the mobile phase A is increased from 41% to 60%, and the ratio of the mobile phase B is decreased from 59% to 40%;
50-65 min, the ratio of the mobile phase A is kept 60%, and the ratio of the mobile phase B is kept 40%.
Further, in some embodiments of the present application, in the above-described instrumental analysis step, nadir, thioidenafil, sildenafil, deluximab, dapoxetine hydrochloride, and rimonafil are used as a class of substances; amino tadalafil, hydroxyHaemoxidanafil citrate, fluoxetine hydrochloride, vardenafil, sertraline hydrochloride and pseudo vardenafil are used as the second substances;
when the detection screening object is a substance in the sample, the pH of the mobile phase B is regulated to 2.5-5.5 by glacial acetic acid, and the detection wavelength is 254nm;
when the detection screening object is the second-class substance in the sample, the pH of the mobile phase B is regulated to 6.5-7.5 by glacial acetic acid, and the detection wavelength is 238nm.
Further, in some embodiments of the present application, the solid sample is any pharmaceutically acceptable solid preparation such as a capsule, a tablet, a granule, and the like.
On the other hand, the embodiment of the application also provides application of the method for detecting PDE5 and SSRI in detecting foods, health products or Chinese patent medicines.
Compared with the prior art, the embodiment of the application has at least the following advantages or beneficial effects:
According to a first aspect, embodiments of the present application provide a method for detecting PDE5 and SSRI, which can process different solid or liquid samples, and adopt a high performance liquid chromatography-diode array detection (HPLC-PDA) technology, so as to detect and analyze PDE5 and SSRI inhibitor substances contained in the samples through peak retention time and ultraviolet characteristic spectrograms, and further judge whether such substances are added in foods, health products and Chinese patent medicines. The detection method is simple, low in cost, good in separation efficiency, accurate in quantification, good in repeatability and strong in specificity, and has extremely high application value.
Aiming at the second aspect, the embodiment of the application also provides application of the method for detecting PDE5 and SSRI in detecting foods, health products or Chinese patent medicines, and the detection method can be used for detecting foods, health products and Chinese patent medicines with kidney tonifying and yang strengthening functions in the market to judge whether PDE5 and SSRI inhibitor components are contained in the foods, health products and Chinese patent medicines, so that technical support is provided for safety supervision of products in the market to ensure rights of consumers.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings that are needed in the embodiments will be briefly described below, it being understood that the following drawings only illustrate some embodiments of the present application and therefore should not be considered as limiting the scope, and other related drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a diagram showing the results of a proprietary verification experiment in test example 1 of the present application;
FIG. 2 is a graph showing the results of the test conducted in accordance with the embodiment 2 of the present application;
FIG. 3 is a graph showing the results of the test conducted in accordance with the comparative example 1 of test example 2 of the present application;
FIG. 4 is a graph showing the results of the test conducted in accordance with the comparative example 2 of the present application;
FIG. 5 is a graph showing the results of the test conducted in accordance with the comparative example 3 of test example 2 of the present application;
FIG. 6 is a chromatogram of the standard protocol of test example 3 of the present application;
FIG. 7 is a chromatogram of the embodiment of example 1 in test example 3 of the present application.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present application more clear, the technical solutions of the embodiments of the present application will be clearly and completely described below. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
It should be noted that the term "comprises," "comprising," or any other variation thereof is intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising … …" does not exclude the presence of other like elements in a process, method, article, or apparatus that comprises an element as described above.
It should be noted that, without conflict, the embodiments of the present application and features of the embodiments may be combined with each other.
The present application will be described in detail with reference to specific examples.
Example 1
The present embodiment provides a method of detecting PDE5 and SSRI comprising the steps of:
Grouping: as a class of substances, nadir, erythronafil, sildenafil, deluximab, dapoxetine hydrochloride, thioidenafil, and namolfrail;
Amino tadalafil, hydroxyHaemoxidanafil citrate, fluoxetine hydrochloride, vardenafil, sertraline hydrochloride and pseudo vardenafil are used as the second substances.
Standard solution preparation: and preparing a mixed reference substance stock solution I of the substances by using acetonitrile, wherein the mass concentration of each component of the substances in the mixed reference substance stock solution I is 400 mug/mL. 0.125 mL, 0.25 mL, 0.5mL, 1mL, 2 mL, 5mL and 10mL of the mixed reference stock solution I are respectively taken, and diluted to 10mL by acetonitrile to obtain a mixed standard series solution I: s 1-s 7, the series of solutions are used for measuring the linear relation of 7 components in a class of substances;
And preparing a mixed reference substance stock solution II of the above two types of substances by using acetonitrile, wherein the mass concentration of each component of the two types of substances in the mixed reference substance stock solution II is 250 mug/mL. Taking 0.1 mL, 0.2 mL, 0.4 mL, 1 mL, 2 mL, 5 mL and 10mL from the mixed reference stock solution II, and diluting with acetonitrile to 10mL to obtain mixed standard series solution II: q1 to q7, the series of solutions being used to determine the linear relationship of the other 7 components; the mixed standard series solution I and the mixed standard series solution II are prepared in an existing mode.
Sample treatment: taking a sample to be tested, adding acetonitrile, performing ultrasonic treatment, cooling to room temperature, performing centrifugal treatment, and taking supernatant to filter to obtain a sample solution to be tested;
wherein, when the sample to be measured is a liquid sample: taking 100ml of liquid sample, fully and uniformly mixing, precisely weighing 10ml, placing in a 50ml volumetric flask, adding 30ml of acetonitrile, performing ultrasonic treatment at a power of 300W and a frequency of 40kHz for 15min, cooling to room temperature, then fixing the volume to 50ml by using acetonitrile, performing centrifugal treatment at a rotating speed of 7000r/min for 5min at a temperature of 20 ℃, and filtering the supernatant by using a microporous organic filter membrane of 0.22 mu m to obtain a sample solution to be tested;
When the sample to be detected is a solid sample, taking a sample with the dosage of 10 times according to the dosage regulated by the sample, grinding and mixing uniformly, precisely weighing the sample with the dosage of 1 time, placing the sample into a 50ml volumetric flask, adding 30ml of acetonitrile, performing ultrasonic treatment for 15min at 300W power and 40kHz frequency, cooling to room temperature, then using acetonitrile to fix the volume to 50ml, performing centrifugal treatment for 5min at 7000r/min, filtering the supernatant with a 0.22 mu m microporous organic filter membrane, and obtaining a sample solution to be detected;
Wherein the sample to be detected is food, health care product or Chinese patent medicine; the solid sample is any pharmaceutically acceptable solid preparation such as capsules, tablets, granules and the like.
Instrument analysis: detecting the sample solution to be tested by using HPLC-PDA equipment, and detecting PDE5 substances and SSRI substances contained in the sample; wherein the SSRI is dapoxetine hydrochloride, fluoxetine hydrochloride and sertraline hydrochloride, the PDE5 is nadifene, erythronafil, thioidenafil, sildenafil, deluxifen, namidenafil, amino tadalafil, hydroxydeluxifen citrate, vardenafil, pseudo-vardenafil;
The liquid chromatography conditions during detection are as follows: adopting a C 18 column with the specification of 250 multiplied by 4.6mm and 5 mu m as a chromatographic column; mobile phase A is acetonitrile, mobile phase B is 10mmol/L ammonium acetate aqueous solution containing 0.1% triethylamine; the column temperature is 30-35 ℃, the sample injection volume is 5-10 mu L, and the flow rate is as follows: gradient elution was performed for 65min at 1.0mL/min, and the gradient elution procedure is as shown in Table 1: the gradient elution program table shows:
table 1: gradient elution program table
When the detection screening object is a substance in the sample, the pH of the mobile phase B is regulated to 2.5-5.5 by glacial acetic acid, the detection wavelength is 254nm, and the chromatographic condition is taken as a chromatographic condition I;
when the detection and screening object is the second kind of substance in the sample, the pH of the mobile phase B is regulated to 6.5-7.5 by glacial acetic acid, the detection wavelength is 238nm, and the chromatographic condition is taken as chromatographic condition II
Negative sample control solution configuration: and taking samples which are determined to contain no first-class substances and no second-class substances, and preparing a negative sample control solution according to the method of the sample treatment step.
Qualitative analysis is carried out by using the retention time of the compound and an ultraviolet characteristic spectrogram, and quantitative detection is carried out by using an external standard method.
And adding the mixed reference substance solution into the sample which is determined to be positive preliminarily, and determining that the sample is positive if the suspected peak in the sample can completely coincide with the chromatographic peak of the reference substance and the similarity of the ultraviolet absorption characteristic spectrogram of the suspected peak and the chromatographic peak of the reference substance is greater than 99.0 percent. Preparing a reference substance solution of the detected components, enabling the chromatographic peak area of the reference substance to be close to the peak area of the detected components in the positive sample, and calculating the content of the detected components in the positive sample by an external standard method.
Example 2
This embodiment is based on embodiment 1, with the difference that:
Sample treatment: weighing 20 capsule samples, cutting the content and the capsule shell, grinding in a mortar, and mixing. Taking out a sample corresponding to 1 dose (2 grains), placing in a 50ml volumetric flask, adding 30ml acetonitrile, performing ultrasonic treatment at 300W power and 40kHz frequency for 15min, cooling to room temperature, fixing volume with acetonitrile to 50ml, centrifuging at 7000r/min for 5min at 20deg.C, and filtering supernatant with 0.22 μm microporous organic filter membrane. Taking the filtrate as a sample solution.
The liquid chromatography conditions at the time of detection were as follows:
Chromatographic condition i:
Chromatographic column: AGILENT HC-C 18 (2) column (250X 4.6mm,5 μm);
Mobile phase a: acetonitrile
Mobile phase B:10mmol/L ammonium acetate solution (containing 0.1% triethylamine, glacial acetic acid to adjust pH to 5.0);
flow rate: 1.0 mL/min;
Column temperature: 30 ℃;
sample injection amount: 10 mu L
Chromatographic condition II:
Chromatographic column: AGILENT HC-C 18 (2) column (250X 4.6mm,5 μm);
Mobile phase a: acetonitrile
Mobile phase B:10mmol/L ammonium acetate solution (containing 0.1% triethylamine, glacial acetic acid to adjust pH to 7.0);
flow rate: 1.0 mL/min;
Column temperature: 30 ℃;
sample injection amount: 10 mu L
The rest of the procedure is the same as in example 1.
Comparative example 1
This comparative example is based on example 2, and differs from example 2 in that: acetonitrile of the organic phase was changed to methanol.
Comparative example 2
This comparative example is based on example 2, and differs from example 2 in that: the pH of mobile phase B was 6.0 in both chromatographic conditions I and II.
Comparative example 3
This comparative example is based on example 2, and differs from example 2 in that: the column temperature of the column was changed to 25 ℃.
Test example 1
The method provided in example 1 is used for processing, detecting and analyzing samples to be tested, wherein the samples to be tested are from 20 batches of conventional commercial kidney-tonifying and yang-strengthening foods, health products, chinese patent medicine products and 30 batches of samples of the same type containing the illicitly added PDE5 and SSRI medicines, and the sample dosage forms comprise capsules, tablets, oral liquid, functional beverages, solid beverages and health wine.
The reagents and instruments used in the test were as follows:
Nardosnafil (lot number: 52039-201902, content: 96.5%); thioidenafil (lot number: 520048-202002, content 99.3%); sildenafil (lot number: 510068-202102, content 100%); haomaxidenafil (lot number: 520046-202002, content 99.7%); namoxidec (lot number: 520040-202102, content: 99.4%); hydroxyl citric acid deluxe (batch number: 510032-201301, content: 98.8%); tadalafil (lot number: 510170-202102, content: 99.8%); vardenafil (lot number: 510169-202001, content: 99.7%); sertraline hydrochloride (lot number: 100702-202103, content: 99.9%); pseudo vardenafil (lot number: 52041-202202, content: 100%); fluoxetine hydrochloride (lot number: 100513-202203, content: 99.8%); amino tadalafil (lot number 520042-202002, content 99.5%) was purchased from chinese food and drug verification institute; dapoxetine hydrochloride (lot number 23071, 99.02%) was purchased from Hong Kong Institute of standard substance, china.
Acetonitrile (chromatographic purity, sigma,); methanol (chromatographic purity, sigma,); ammonium acetate (chromatographic purity, western chemical industries, ltd.); triethylamine (chromatographic purity, kemi euro chemical company,); glacial acetic acid (chromatographic purity, kemi Euro chemical Co., ltd.) the water used for the experiment was ultrapure water.
SHIMADZU LC-2050C 3D high performance liquid chromatograph (Shimadzu corporation, japan equipped with PDA detector); mettler Toledo XSE205 electronic balance (meltrele-tolido company, switzerland); JP-060S-type ultrasonic apparatus (Shenzhen clean Equipment Co., ltd.); eppendor 5430R high-speed refrigerated centrifuge (Germany Ai Bende Co.) SevenMulti pH meter (Mertrex-Toli Co., switzerland); ULPHW-IV ultra pure water instrument (Sichuan Utility ultra pure water technologies Co., ltd.).
In the test example, the reference numerals 1 to 14 marked in all the maps respectively correspond to 14 chemical drugs, and specifically: 1. nardosnafil; 2. hongdafil; 3. sildenafil; 4. haomaxidenafil; 5. dapoxetine hydrochloride; 6. thioidenafil; 7. namsildenafil; 8. amino tadalafil; 9. tadalafil; 10. hydroxyl citric acid deluxe; 11. fluoxetine hydrochloride; 12. vardenafil; 13. sertraline hydrochloride; 14. pseudo vardenafil.
And (3) methodological verification:
the analysis method of four parts 9101 of the 2020 edition of Chinese pharmacopoeia is used for verifying the guiding principle to investigate the items such as the specificity, the linearity, the detection limit, the quantitative limit and the like of the HPLC, and the results all meet the corresponding requirements; the method comprises the following steps:
and (3) specificity verification:
The mixed control solution, the negative sample solution and the negative sample addition standard solution were analyzed according to the chromatographic conditions in example 1, respectively. The experimental results are shown in fig. 1, the main chromatographic peaks of the impurities of the negative sample and the 14 kidney-tonifying yang-strengthening chemical drugs have no overlapping in retention time, and the interference of matrix effect on detection can be eliminated through a PDA spectrogram. Therefore, the method has better specificity.
Linear relationship investigation, detection limit and quantification limit:
And respectively analyzing the mixed standard series solution I and the mixed standard series solution II, drawing a standard curve by taking the mass concentration (mug/mL) as an abscissa (x) and the peak area as an ordinate (y), and establishing a linear regression equation. The 14 kinds of kidney-tonifying yang-strengthening chemical drugs all show good linear relations in respective linear ranges, and a linear regression equation and a correlation coefficient (r) are shown in table 2: linear relation investigation, detection limit and quantitative limit result data table. All correlation coefficients (r) are equal to or greater than 0.9999;
the reference substance solution is diluted step by step, and the concentrations of the reference substance solution with the signal to noise ratio R SN more than or equal to 3 and the signal to noise ratio R SN more than or equal to 10 are respectively used as a detection Limit (LOD) and a quantification Limit (LOQ). LOD and LOQ for each drug are shown in Table 2.
Table 2: linear relation investigation, detection limit and quantitative limit result data table
Recovery rate test:
The negative samples without 14 kinds of kidney-tonifying yang-strengthening chemical medicines are precisely weighed for about one dose, 9 parts are divided into 3 groups, and 3 parts are divided into each group. Adding different amounts of mixed reference substance stock solution I or mixed reference substance stock solution II into each group of samples, preparing into three standard adding concentration levels (specific standard adding concentrations are shown in a table 3: a recovery test result data table, wherein in the table 3, standard adding concentration parts of each compound are respectively in the low, medium and high standard adding concentration levels from top to bottom) according to the method in the embodiment 1, adding standard adding solutions into negative samples with concentration ranges of s3 (20 mu g/mL), s4 (40 mu g/mL), s5 (80 mu g/mL), q3 (10 mu g/mL), q4 (25 mu g/mL) and q5 (50 mu g/mL), and carrying out detection analysis, and drawing a chromatogram. The standard recovery and Relative Standard Deviation (RSD) of 14 chemicals for tonifying kidney and strengthening yang in each standard solution were calculated.
The results are shown in Table 3: the recovery rate test result data table shows; the results show that the recovery rate of all medicines is between 97.8 and 102.8 percent, and the RSD is less than 2 percent (n=3 or n=9), which proves that the method has better accuracy.
Table 3: recovery test result data sheet
Precision test:
Instrument precision: sucking the standard adding concentration of the negative sample standard adding solution in the same recovery rate test in the mixed reference substance I group at the s4 (40 mu g/mL) level, the standard adding concentration of the mixed reference substance II group at the q4 (25 mu g/mL) level, continuously measuring for 6 times according to the chromatographic conditions in the embodiment 1, recording the peak areas of 14 target components, and calculating the RSD. The results showed that RSD (n=6) of peak areas of the chromatographic peaks of nadir, sildenafil, hamoxidecil, dapoxetine hydrochloride, thioidenafil, nadir, amino tadalafil, hydroxydeluxifen citrate, fluoxetine hydrochloride, vardenafil, sertraline hydrochloride, pseudo-vardenafil were 0.57%, 0.52%, 0.51%, 0.49%, 0.33%, 0.47%, 0.48%, 0.64%, 0.70%, 1.18%, 0.76%, 0.77%, 0.52%, 0.68%, respectively, indicating good precision of the instrument.
Intra-day precision and inter-day precision: respectively preparing a mixed reference substance solution I and a mixed reference substance solution II with 3 concentration levels, wherein the concentration ranges are respectively s1 (5 mu g/mL), s4 (40 mu g/mL), s7 (400 mu g/mL) and q1 (2.5 mu g/mL), q4 (25 mu g/mL) and q7 (250 mu g/mL), and measuring once every 4 hours, and continuously measuring for 24 hours to serve as an intra-day precision test; every 12 hours for 3 consecutive days as a daily precision test. The peak area RSD of each component was calculated.
The results are shown in Table 4: the data sheet of the precision test result shows that the method has good precision.
Table 4: precision test result data table
Repeatability test:
Taking positive samples containing the PDE5 and SSRI drugs illegally added in the same batch, independently preparing 6 parts of test solution according to the method of the example 1, detecting and analyzing, and calculating the content by an external standard method respectively, wherein the content of sildenafil is 9.87 mg/granule, and the RSD (n=6) is 1.1%, thus showing that the method has good repeatability.
Stability test:
And taking a negative sample adding standard solution (the adding standard concentration of the mixed reference substance I group is about 40 mu g/mL, the adding standard concentration of the mixed reference substance II group is about 25 mu g/mL) in the same recovery rate test, respectively analyzing 0,2, 4, 8, 12 and 24 hours after preparation, and recording the peak areas of all the components. The calculation results showed that the peak areas RSD (n=6) of the 14 target components were 0.49% to 1.08% within 24 hours, indicating that the sample solutions were relatively stable within 24 hours.
Test example 2
The corresponding relation of the reagent source and instrument selected in the test example and the reference numbers in the map is the same as that in test example 1;
The sample was tested as described in example 2, and the test results are shown in FIG. 2, which is effective for qualitative and quantitative analysis of PDE5 and SSRI class substances in 14 contained in the sample.
Meanwhile, the samples were examined according to the methods of comparative examples 1 to 3, and the results are shown in FIGS. 3 to 5, respectively.
From the results, it can be concluded that:
In the case of comparative example 1, since the eluting power of methanol was relatively weak, 14 target compounds could not be all eluted when methanol alone was used (as shown in fig. 3), whereas 14 compounds were all eluted when acetonitrile was used, and baseline separation was achieved.
In the case of comparative example 2, the pH of the mobile phase directly influences the form in which the compound is present (either all in molecular form or all in ionic form or both), thereby altering the retention behavior of the compound on the chromatographic column and thus affecting the separation of the compound. As shown in fig. 4, sildenafil and mmlung sildenafil cannot be effectively separated when pH of mobile phase B in chromatographic condition i is 6.0, more than 5.5. When the pH of mobile phase B in chromatographic condition ii was 6.0, less than 6.5, the baseline separation was not achieved for tadalafil and hydroxymatazanil citrate and two pairs of compounds fluoxetine hydrochloride and vardenafil. In addition, the tolerance pH of the general chromatography is 2-8, and when the pH is below 2 or above 8, the column damages the bonding phase of the chromatographic column, so that the column efficiency is reduced and the service life of the chromatographic column is shortened. Therefore, comprehensively considering the separation effect of each compound, the universality and the economic cost of the method, the pH value of the chromatographic condition I is selected to be 2.5-5.5, and the pH value of the chromatographic condition II is selected to be 6.5-7.5.
In the scheme of comparative example 3, different column temperatures affect the strength of retention of the compound on the chromatographic column, and thus the separation effect of the compound. As shown in fig. 5, tadalafil and hydroxymatazanil citrate completely coincide and cannot be separated at 25 ℃; sildenafil and deluxe also cannot be separated effectively. But when the temperature is above 35 deg.c, the service life of the chromatographic column is reduced. Therefore, the column temperature of the chromatographic column is selected to be 30-35 ℃ by comprehensively considering the economic cost and the separation degree of the compounds.
Test example 3
The corresponding relation of the reagent source and instrument selected in the test example and the reference numbers in the map is the same as that in test example 1;
As shown in fig. 6, the SSRI, PDE5 species chromatogram obtained according to the national food and drug administration recommended standard BJS2009030 protocol;
as shown in FIG. 7, the SSRI, PDE5 class material chromatogram obtained according to the method of example 1 of the present application is shown.
Compared with the prior art, three SSRI substances (fluoxetine hydrochloride, dapoxetine hydrochloride and sertraline hydrochloride) related to the scheme of the application cannot be detected in the standard method, the scheme of the application has better separation effect on the other 11 PDE5 drugs, and the hydroxy deluxe and sildenafil in the standard scheme cannot achieve baseline separation. Therefore, the quantitative accuracy of the scheme of the application is higher, and the application range is wider.
In summary, the embodiment of the application provides a method for detecting PDE5 and SSRI and application thereof, which are applied to foods, health products and Chinese patent medicines, and can detect and analyze PDE5 and SSRI inhibitor substances contained in a sample so as to judge whether the product is illegally added with the compounds or not, thereby guaranteeing the rights and interests of consumers; the detection method is simple, low in cost, good in separation efficiency, accurate in quantification, good in repeatability and strong in specificity, and has extremely high application value.
The embodiments described above are some, but not all embodiments of the application. The detailed description of the embodiments of the application is not intended to limit the scope of the application, as claimed, but is merely representative of selected embodiments of the application. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without making any inventive effort, are intended to be within the scope of the application.
Claims (4)
1. A method for detecting PDE5 and SSRI, comprising the steps of:
sample treatment: taking a sample to be tested, adding acetonitrile, performing ultrasonic treatment, cooling to room temperature, performing centrifugal treatment, and taking supernatant to filter to obtain a sample solution to be tested;
Instrument analysis: detecting the sample solution to be tested by using HPLC-PDA equipment, and detecting PDE5 substances and SSRI substances contained in the sample;
in the sample processing step, the sample to be detected is a liquid sample or a fixed sample;
when the sample to be measured is a liquid sample: placing 10ml of liquid sample into a 50ml volumetric flask, adding 30ml of acetonitrile, performing ultrasonic treatment, cooling to room temperature, then fixing the volume to 50ml, performing centrifugal treatment, and taking supernatant to filter to obtain a sample solution to be tested;
When the sample to be detected is a solid sample, grinding and crushing the solid sample, taking the crushed solid sample which is equal to the once oral dosage of the sample, placing the solid sample into a50 ml volumetric flask, adding 30ml acetonitrile, performing ultrasonic treatment, cooling to room temperature, then fixing the volume to 50ml, performing centrifugal treatment, and taking supernatant to filter to obtain a sample solution to be detected;
In the instrument analysis step, SSRI substances are dapoxetine hydrochloride, fluoxetine hydrochloride and sertraline hydrochloride;
PDE5 class substances are nadiferin, erythronafil, thioidenafil, sildenafil, deluxifen, namoscilafil, amino tadalafil, hydroxydeluxifen citrate, vardenafil and pseudo-vardenafil;
in the instrument analysis step, the liquid chromatography conditions are as follows: adopting a C 18 column with the specification of 250 multiplied by 4.6mm and 5 mu m as a chromatographic column; mobile phase A is acetonitrile, mobile phase B is 10mmol/L ammonium acetate solution containing 0.1% triethylamine; the column temperature is 30-35 ℃, the sample injection volume is 5-10 mu L, and the flow rate is as follows: gradient elution is carried out for 65min at a concentration of 1.0 mL/min;
In the instrument analysis step, nadir, thioidenafil, sildenafil, deluximab, dapoxetine hydrochloride and rimocaine hydrochloride are taken as substances; amino tadalafil, hydroxyHaemoxidanafil citrate, fluoxetine hydrochloride, vardenafil, sertraline hydrochloride and pseudo vardenafil are used as the second substances;
when the detection screening object is a substance in the sample, the pH of the mobile phase B is regulated to 2.5-5.5 by glacial acetic acid, and the detection wavelength is 254nm;
When the detection screening object is the second-class substance in the sample, the pH value of the mobile phase B is regulated to 6.5-7.5 by glacial acetic acid, and the detection wavelength is 238nm;
in the instrument analysis step, the gradient elution procedure is as follows:
0-8 min, the ratio of the mobile phase A is increased from 10% to 30%, and the ratio of the mobile phase B is decreased from 90% to 70%;
8-16 min, the ratio of the mobile phase A is increased from 30% to 37%, and the ratio of the mobile phase B is decreased from 70% to 63%;
16-23 min, the ratio of the mobile phase A is kept 37%, and the ratio of the mobile phase B is kept 63%;
23-23.1 min, the ratio of the mobile phase A is increased from 37% to 41%, and the ratio of the mobile phase B is decreased from 63% to 59%;
23.1-28 min, the ratio of the mobile phase A is kept 41%, and the ratio of the mobile phase B is kept 59%;
28-50 min, the ratio of the mobile phase A is increased from 41% to 60%, and the ratio of the mobile phase B is decreased from 59% to 40%;
50-65 min, the ratio of the mobile phase A is kept 60%, and the ratio of the mobile phase B is kept 40%.
2. The method of claim 1, wherein in the sample processing step, the sample is sonicated at a power of 300W at a frequency of 40kHz for 15min; centrifuging at 20deg.C at 7000r/min for 5min; the supernatant was filtered through a 0.22 μm microporous organic filter.
3. The method of claim 1, wherein the solid sample is any pharmaceutically acceptable solid formulation such as a capsule, a tablet, a granule, etc.
4. Use of a method for detecting PDE5 and SSRI according to any one of claims 1 to 3 in the detection of food, health products or chinese patent medicine.
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