CN101566608B - Method for detecting paracetamol added to Chinese patent medicines illegally - Google Patents
Method for detecting paracetamol added to Chinese patent medicines illegally Download PDFInfo
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Abstract
The invention discloses a method for detecting paracetamol added to compounds illegally, and the method comprises the following steps: the structure of the paracetamol is corroborated by using a high efficiency liquid chromatography-mass spectrometry method through monitoring the following ions: parent ions 152.1, daughter ions 110.1 and daughter ions 93.1, and the paracetamol content is determined by using the high efficiency liquid chromatography method. In the method, the structure of the detected paracetamol is corroborated by detecting the three kinds of ions by using the high efficiency liquid chromatography-mass spectrometry method, and the detected conclusion is accurate; the method gropingly optimizes various experiment conditions and has the advantages of strong specialization, high sensitivity and accuracy, good stability and strong practicability, therefore, the method has wide application prospect in detecting the paracetamol which is added to Chinese patent medicines illegally.
Description
Technical field
The present invention relates to Pharmaceutical Analysis detection technique field, particularly the method for paracetamol in the detection composition.
Background technology
Medicine is that the mankind are used to the specialty goods that prevents, treat, diagnose the illness, is related to consumers in general's drug safety, health, therefore need implement effectively supervision to it.Chinese patent drug should be to be raw material with the Chinese herbal medicine, processes the Chinese herbal product of various different dosage forms through preparation processing, comprises ball, looses, cream, red various formulations.But the banner that spraying pure Chinese medicine at present, has no side effect is added the behavior of medicinal chemicals or the fraud of finished product Western medicine secretly and is emerged in an endless stream; Because chemical raw material kind, quantity, the toxicity of mixing are not known; The safety of taking the people can't ensure, to the individual, society has been caused serious harm.
The illegal paracetamol that adds possibly cause the patient agranulocytosis, methemoglobinemia, allergic dermatitis (fash, pruitus etc.), hepatitis, decrease of platelet etc. take place in Chinese patent drug; Therefore; Need set up the illegal paracetamol that adds in the Chinese patent drug of high-efficiency method test section; In time find the drug quality problem, eliminate drug safety hidden danger as early as possible.The paracetamol assay method of bibliographical information has volumetric analysis, ultraviolet spectrophotometry and high performance liquid chromatography.Owing to be difficult to paracetamol is extracted from Chinese patent drug, volumetric analysis and ultraviolet spectrophotometry all are not suitable for the mensuration of paracetamol in the traditional Chinese medicine complex system.
Summary of the invention
The method that the purpose of this invention is to provide the illegal paracetamol content that adds in a kind of detection composition.
The method of paracetamol in the detection composition provided by the present invention; Comprise the steps: to carry out the discriminating and the structural identification of the paracetamol in the composition through monitoring following ion with high performance liquid chromatography-mass spectrometry method: parent ion 152.1, daughter ion 110.1 and daughter ion 93.1, carry out the assay of paracetamol with high performance liquid chromatography.
In said high performance liquid chromatography-mass spectrometry method, the water of the moving phase of employing can be the 10-50mmol/L ammonium acetate solution, and organic phase specifically can be methyl alcohol; Said water is preferably the 10mmol/L ammonium acetate solution.
The most handy said moving phase is carried out gradient elution in said high performance liquid chromatography-mass spectrometry method; The starting point of said moving phase is 95% volume water: 5% volume organic phase; The point of middle process comprises 20% volume water: 80% volume organic phase, terminal point are 95% volume water: 5% volume organic phase.
In said high performance liquid chromatography-mass spectrometry method, ion gun: electrospray ionization source; Scan pattern: reaction of high order monitoring; Polarity: kation; And impact energy: 10～20V.
The water of the moving phase in the said high performance liquid chromatography can be 0.1～0.5% (quality percentage composition) phosphate aqueous solution, and organic phase is a methyl alcohol; Said water is preferably 0.1% phosphate aqueous solution.
Carry out gradient elution with said moving phase in the said high performance liquid chromatography, the volume ratio of water and organic phase is (89%～92%) in the starting point of said moving phase and the terminal point: (11%～8%).
Comprise the steps: in the said high performance liquid chromatography said composition to be extracted, obtain extract, said extract is carried out said high performance liquid chromatography detect with 50%-70% (volumn concentration) methanol solution.
Said composition can be the Chinese patent drug composition, specifically can be type of curing cold Chinese patent drug composition or antirheumatic Chinese patent drug composition.
High performance liquid chromatography in the inventive method-mass spectrometry method makes the structure of paracetamol obtain conclusive evidence through the detection of 3 kinds of quasi-molecular ions, and check conclusion is accurate; The inventive method has carried out groping optimizing to various experiment conditions, and the method specificity is strong, and is highly sensitive, accuracy is high, and good stability is practical.Because Chinese medicine illegally adds the illegal phenomenon of chemicals and also will continue, and the development of analysis and detection technology fails to surmount the speed of development of mingling false making generally.To the illegal research work of adding of chemicals in the Chinese patent drug that cures cold, be initiative to the detection method of present drug safety supervision new situations and new problems.Therefore, the inventive method will have broad application prospects in the illegal interpolation paracetamol of compositions such as Chinese patent drug detects.
Description of drawings
Fig. 1 is the product ion figure of paracetamol.
Fig. 2 is total ion current figure under the reaction of high order monitoring pattern.
Fig. 3 extracts mass spectrogram down for the reaction of high order monitoring pattern.
Fig. 4 is paracetamol cracking process figure.
Fig. 5 is a high-efficient liquid phase chromatogram.
Embodiment
Employed experimental technique is conventional method like no specified otherwise among the following embodiment.
Used material, reagent etc. like no specified otherwise, all can obtain from commercial sources among the following embodiment.
The selection of embodiment 1, experimental technique and effect detection
Reference substance (paracetamol) is available from Nat'l Pharmaceutical & Biological Products Control Institute.
One, the selection of experimental technique
(1) paracetamol high performance liquid chromatography-mass spectrometry structural identification
Chromatographic condition: use octadecylsilane chemically bonded silica to be filling agent; With the 10-50mmol/L ammonium acetate solution is mobile phase A, is Mobile phase B with methyl alcohol, carries out gradient elution.
Mass spectrum condition: triple quadrupole bar type mass spectrometer; Ion gun: electrospray ionization source; Scan pattern: reaction of high order monitoring; Polarity: kation; Electron-multiplier voltage gain: 800V; Dry gas temperature: 350 ℃; Dry gas flow velocity: 91/min; Atomizer pressure: 40Psi; Capillary voltage: 4000V; Parent ion: 152.1; Daughter ion: 110.1; Daughter ion: 93.1; Impact energy: 10～20V; Ion transfer voltage: 100V.
The preparation of reference substance solution: the paracetamol reference substance is dissolved in methyl alcohol, processes the solution that every 1ml contains 10 μ g; Get above-mentioned solution 5ml, put in the 100ml volumetric flask, add 10～50mmol/L ammonium acetate solution and be diluted to 100ml, obtain reference substance solution.
The preparation of need testing solution: get test sample powder 0.1g, add methyl alcohol 25ml, ultrasonic 15 minutes, filter, get filtrating 5ml, put in the 10ml volumetric flask, add 10～50mmol/L ammonium acetate solution, be diluted to 10ml.
Determination method: accurate respectively reference substance solution 3 μ l and the need testing solution 5 μ l of drawing, inject high performance liquid chromatography-GC-MS.
(2) high performance liquid chromatography content determination selection of experiment conditions:
1, detects the selection of wavelength
Paracetamol reference substance (the about 0.1mg/ml of concentration) scans in 190～370nm wavelength coverage, at the 243nm place absorption maximum is arranged, so confirm that detecting wavelength is 243nm.
2, the selection of moving phase
Moving phase sample separation with different proportion; When the ratio of moving phase is the mixed solution of phosphate aqueous solution (89～92%)-methyl alcohol (11～8%), separate better (volume ratio of water and organic phase is (89～92%): (11～8%)), the negative control sample is noiseless at the corresponding appearance time of paracetamol place; But complicated component in the test sample treats that the paracetamol peak goes out other component with the gradient elution wash-out after rolling again.
3, extract choice of Solvent
Get the sample of same lot number, add Different concentrations of alcohol, each 25ml of methyl alcohol, sonicated 15 minutes is measured, and the result shows that 50%～70% methanol aqueous solution extraction effect is good, and 50% methanol aqueous solution is best.
4, chromatographic condition and system suitability test: use octadecylsilane chemically bonded silica to be filling agent; With 0.1～0.5% phosphate aqueous solution is mobile phase A, is Mobile phase B with methyl alcohol, carries out gradient elution; Detect wavelength 243nm.
Two, the detection of experiment effect
(1) concrete experimental technique
1. high performance liquid chromatography-mass spectrometry method:
High-efficient liquid phase chromatogram condition: ZORBAX SB-C18 (2.1 * 50mm, 3.5 μ m) chromatographic column, the filling medium is an octadecylsilane chemically bonded silica; 30 ℃ of column temperatures are mobile phase A with the 10mmol/L ammonium acetate solution, are Mobile phase B with methyl alcohol, and according to the form below carries out gradient elution, flow velocity 0.3ml/min.
Table 1, gradient elution step
Mass spectrum condition: ion gun: electrospray ionization source; Scan pattern: reaction of high order monitoring; Polarity: kation; Electron-multiplier voltage gain: 800V; Dry gas temperature: 350 ℃; Dry gas flow velocity: 9l/min; Atomizer pressure: 40Psi; Capillary voltage: 4000V; Parent ion: 152.1; Daughter ion: 110.1; Daughter ion: 93.1; Ion transfer voltage: 100V; Impact energy: 15V.Residence time 150ms; Sweep time: 0min-pump stand-by time.
The preparation of reference substance solution: take by weighing the paracetamol reference substance, add methyl alcohol and process the solution that every 1ml contains 10 μ g, measure above-mentioned solution 5ml, put in the 100ml volumetric flask, add the 10mmol/L ammonium acetate solution and be diluted to 100ml.
The preparation of need testing solution: get test sample powder 0.1g, add methyl alcohol 25ml, ultrasonic 15 minutes, filter, get filtrating 5ml, put in the 10ml volumetric flask, add the 10mmol/L ammonium acetate solution, be diluted to 10ml.
According to the said method test, the primary product ion is 110.1,93.1; The product ion figure of paracetamol is best during impact energy 15V, sees Fig. 1, and derivation paracetamol product ion 110.1 is preponderated.3 identification points confirming the reaction of high order monitoring in view of the above are parent ion 152.1; Product ion: 110.1,93.1.
2, paracetamol assay
The preparation of reference substance solution: the paracetamol reference substance is dissolved in 50% methanol solution, processes the solution that every 1ml contains 10 μ g, obtain reference substance solution.
The preparation of need testing solution: get test sample powder 0.5g, add 50% methanol aqueous solution 25ml, sonicated 15 minutes is filtered, and gets filtrating, obtains need testing solution.
Determination method: draw reference substance solution and need testing solution 10 μ l respectively, inject liquid chromatograph, measure, calculate the content of paracetamol with external standard method.
Chromatographic condition: chromatographic column is SUPELCO Discovery
C18 (25cm * 4.6mm; 5 μ m) chromatographic column, the filling medium is an octadecylsilane chemically bonded silica; 35 ℃ of column temperatures;
The gradient elution damping fluid is that the mixed solution of moving phase C and moving phase D: moving phase C is 0.1% phosphate aqueous solution, and moving phase D is a methyl alcohol; Flow velocity is 1ml/min; The gradient elution step is as shown in table 2.
Detecting device is the DAD detecting device, and the detection wavelength is 243nm;
The gradient elution step of table 2, high performance liquid chromatography detection by quantitative
(2) detection of experiment effect
1. LC-MS structural identification method
1.1 specificity test
Get positive test sample, negative test sample and paracetamol reference substance respectively and measure, relatively its total ion current figure according to said method.Total ion current figure is as shown in Figure 2, and (A representes the reference substance paracetamol; B representes positive: Tianjin * * pharmaceutcal corporation, Ltd's sample, C representes negative sample: the Kazakhstan medicine * * pharmaceutical factory's sample), locate to have a peak in the identical time among the positive test sample total ion current of the result figure with paracetamol reference substance total ion current figure main peak; Extract its mass spectrogram; The result as shown in Figure 3 (A representes reference substance, and B representes positive: Tianjin * * the medicine company sample), positive test sample and reference substance are consistent.Negative sample is at no peak, the place of identical time with paracetamol reference substance total ion current figure main peak, and negative sample extracts mass spectrogram does not also have paracetamol parent ion and daughter ion.The paracetamol cracking process is as shown in Figure 4.
2. high performance liquid chromatography content determination
2.1 specificity test
Get positive test sample, negative test sample and paracetamol reference substance respectively and measure, relatively its chromatogram according to said method.Locate to have a peak in the identical time in the positive test sample chromatogram of result with paracetamol reference substance chromatogram main peak; It has been carried out the peak purity analysis; Peak purity is 100.0%, and other component chromatographic peak and Paracetamol peak energy reach baseline separation in the positive test sample chromatogram.And in negative test sample with in the identical time of paracetamol reference substance solution chromatographic peak, locate no chromatographic peak (see accompanying drawing 5, A representes reference substance, and B representes positive, and C representes negative sample).
2.2 the investigation of linear relationship
Take by weighing with the paracetamol reference substance; Add moving phase and process the solution that every 1ml contains paracetamol 1.044mg; As the reference substance solution mother liquor, with mother liquor respectively with the dilution of 50% methyl alcohol as follows: 1ml → 10ml, 2ml → 25ml, 1ml → 25ml, 1ml → 50ml, 1ml → 100ml are as reference substance solution 1～5; Get reference substance solution 5, respectively with the dilution of 50% methyl alcohol as follows: 5ml → 10ml, 2ml → 10ml, 1ml → 10ml are as reference substance solution 6～8, and the accurate respectively 10 μ l of above-mentioned reference substance solution 1～8 that draw inject high performance liquid chromatograph successively; Measure peak area by above-mentioned chromatographic condition, be followed successively by: 4148.98926,3295.86523,1658.55945; 832.39801,414.66922,208.18076,414.66922; 208.18076,83.11439,41.40110; With the peak area integrated value is ordinate, and paracetamol sample introduction concentration (μ g/ml) is horizontal ordinate, the drawing standard curve, and regression equation is:
Paracetamol: Y=39.6337X+0.8179 correlation coefficient r=0.99999
The result shows that paracetamol sample introduction concentration is good linear relationship in 1.044～104.4 μ g/ml scopes.
2.3 precision test (replica test)
Get 6 samples (Shandong * * pharmaceutcal corporation, Ltd 0712051 batch) of same batch, method for distilling is equal to, with the paracetamol of 10 μ g/ml as reference substance solution; Press aforementioned high-efficient liquid phase chromatogram condition replication sample 6 times, contain the amount of paracetamol in the external standard method calculation sample, the mensuration result is: 0.23744; 0.24102,0.24055,0.23946; 0.23687,0.24016mg/g; Average content 0.23925mg/g; RSD=0.72% (n=6), result show that this method repeatability is good.
2.4 accuracy test (average recovery test)
Take by weighing the Shandong that known content is 0.23925mg/g * * the 0712051 lot sample article 0.6g of pharmaceutcal corporation, Ltd; Add paracetamol reference substance 149.75 μ g respectively, press preparation method's operation of sample solution, measure its content; And calculate recovery rate; 6 samples experimentize in getting batch, each sample do 2 parallel, the result takes the mean.The result is as shown in table 3.Recording the recovery is 100.877%, 99.286%, 99.132%, 102.487%, 100.321%, 99.295%, and mean value 100.23%, RSD are 1.3% (n=6).
Table 3, sample pipetting volume recovery test result
2.5 sample solution stability test
Get Shandong of preserving under the room temperature * * 0712051 batch of need testing solution of pharmaceutcal corporation, Ltd, sample introduction is measured peak area at random in 2 days, the peak area integrated value is followed successively by: 442.33331; 440.70630,441.53287,440.91956; 442.73236; 438.16318,438.96237,437.82404; Mean value: 440.39675, RSD (%)=0.43%.Mensuration result shows that sample solution is basicly stable in 2 days.
2.6 confirming of detectability
Contrast solution 8 is down investigated in the line taking sexual intercourse, is diluted to variable concentrations with 50% methanol solution, each sample introduction 10 μ l; When sample introduction concentration was 25.06ng/ml as a result, signal to noise ratio (S/N ratio) was 3: 1, therefore; Can be similar to and think, use this method, the concentration limit of paracetamol is 25ng/ml.
2.7 confirming of quantitative limit
Contrast solution 8 is down investigated in the line taking sexual intercourse, is diluted to variable concentrations with 50% methanol solution, each sample introduction 10 μ l; When sample introduction concentration was 83.52ng/ml as a result, signal to noise ratio (S/N ratio) was 10: 1, therefore; Can be similar to and think, use this method, the minimum quantitative concentrations of paracetamol is 84ng/ml.
Paracetamol in embodiment 2, the detection Chinese patent drug not of the same race
One, Shandong * * pharmaceutcal corporation, Ltd flu * * particle in the detection of paracetamol
(1) high performance liquid chromatography-mass spectrometry carries out qualitative determination
1, the preparation of need testing solution:
Sample thief bag content is weighed, and porphyrize is got powder 0.1g, adds methyl alcohol 25ml, and ultrasonic 15 minutes, filter, get filtrating 5ml, put in the 10ml volumetric flask, add the 10mmol/L ammonium acetate solution, be diluted to 10ml.
2, reference substance solution preparation
The paracetamol reference substance is dissolved in methyl alcohol, processes the solution that every 1ml contains 10 μ g; Get above-mentioned solution 5ml, put in the 100ml volumetric flask, add the 10mmol/L ammonium acetate solution and be diluted to 100ml, obtain reference substance solution.
3, condition determination:
(1) high performance liquid chromatography:
Chromatographic column is ZORBAX SB-C18 (2.1 * 50mm, 3.5 μ m), and the filling medium is an octadecylsilane chemically bonded silica; 30 ℃ of column temperatures;
Gradient eluent is: mobile phase A is the 10mmol/L ammonium acetate solution, and Mobile phase B is a methyl alcohol; Flow velocity is 0.3ml/min; The gradient elution step is as shown in table 4;
Table 4, gradient elution program
(2) mass spectrum
Mass spectrum condition: triple quadrupole bar type mass spectrometer; Ion gun: electrospray ionization source; Scan pattern: reaction of high order monitoring; Polarity: kation; Electron-multiplier voltage gain: 800V; Dry gas temperature: 350 ℃; Dry gas flow velocity: 9l/min; Atomizer pressure: 40Psi; Capillary voltage: 4000V; Parent ion: 152.1; Daughter ion: 110.1; Daughter ion: 93.1; Impact energy: 15V; Ion transfer voltage: 100V; The residence time: 150ms; Sweep time: 0-22min.
4, method:
Get reference substance solution 3 μ l and need testing solution 5 μ l respectively, inject high performance liquid chromatography-GC-MS.
Get the sample of 10 different batches, each batch do 2 parallel, the result takes the mean.
Test sample total ion current figure with the corresponding appearance time of reference substance total ion current figure place, a chromatographic peak is arranged, extract this chromatographic peak mass spectrogram, detect 152.1 → 110.1,152.1 → 93.1, promptly 3 identification points are parent ion 152.1; Product ion: 110.1,93.1.
(2) high performance liquid chromatography quantitative measurement
1, the preparation of need testing solution
Get the sample powder 0.5g in the experiment (), add 50% methanol aqueous solution 25ml, sonicated 15 minutes is filtered, and gets filtrating, obtains need testing solution.
2, the preparation of reference substance solution
The paracetamol reference substance is dissolved in 50% methanol solution, processes the solution that every 1ml contains 10 μ g, obtain reference substance solution.
3, chromatographic condition
Chromatographic column is SUPELCO Discovery
C18 (25cm * 4.6mm; 5 μ m) chromatographic column, the filling medium is an octadecylsilane chemically bonded silica; 35 ℃ of column temperatures;
Gradient eluent is that the mixed solution of moving phase C and moving phase D: moving phase C is 0.1% phosphate aqueous solution, and moving phase D is a methyl alcohol; Flow velocity is 1ml/min; The gradient elution step is as shown in table 5.
Detecting device is the DAD detecting device, and the detection wavelength is 243nm;
The gradient elution step of table 5, high performance liquid chromatography detection by quantitative
4, method:
Get reference substance solution and need testing solution 10 μ l respectively, inject liquid chromatograph, measure, with the content of external standard method with the calculated by peak area paracetamol.
Get the sample of 10 different batches, each batch do 2 parallel, the result takes the mean.
Detect according to said method, according to the content adjustment assay sampling amount of paracetamol.
5, average recovery test
Take by weighing 1/2 of assay sampling amount; Add paracetamol respectively according to the assay result amount of calculating; Carry out the need testing solution preparation according to method described in the step 1, in step, detect the content of paracetamol in the need testing solution under the 1 said condition, and calculate recovery rate.
Experimental result is as shown in table 6.
Table 6, Shandong * * pharmaceutcal corporation, Ltd's flu * * testing result of 11 batches of particles
| Lot number | Average loading amount (g) | Assay sampling amount (g) | Paracetamol content (mg/ bag) | Average recovery (%) |
| 0803057 | 12.2299 | ?0.5 | 6.822 | 100.1％ |
| 0801086 | 11.7905 | ?1 | 3.267 | 99.9％ |
| 0802073 | 12.0023 | ?1 | 3.180 | 99.8％ |
| 0712051 | 12.2045 | ?1 | 2.920 | 100.2 |
| 0602066 | 12.0008 | ?2 | 1.539 | 99.7％ |
| 0802077 | 12.0052 | ?3 | 1.272 | 99.5％ |
| 0801076 | 12.0067 | ?5 | 0.896 | 99.6％ |
| 0609010 | 11.9980 | ?5 | 0.465 | 99.2％ |
| 0803025 | 11.9053 | ?5 | 0.289 | 98.9％ |
| 0802028 | 12.1495 | 5 | 0.196 | 99.3％ |
| 0802023 | 12.2141 | 5 | 0.118 | 98.8％ |
Two, Sichuan * * pharmaceutcal corporation, Ltd flu * * particle in the detection of paracetamol
(1) high performance liquid chromatography-mass spectrometry carries out qualitative determination
Experimental technique is identical with method described in; Difference is: high performance liquid chromatogram-mass spectrometry moving phase water adopts the 20mmol/L ammonium acetate solution, and organic phase adopts methyl alcohol, is mobile phase A with the water; Organic phase is a Mobile phase B, and the gradient elution step is as shown in table 7; Mass spectrum condition impact energy adopts 10V.
Table 7, gradient elution step
(2) high performance liquid chromatography quantitative measurement
Experimental technique is identical with method described in, and difference is: use 70% methanol aqueous solution as extraction agent in the preparation of need testing solution, moving phase C is 0.3% phosphate aqueous solution; The gradient elution step is as shown in table 8.
Table 8, gradient elution step
Get 080101 lot sample article, repeat 2 times, the result takes the mean.The result shows, 080101 batch of flu of this manufacturer production * * detecting paracetamol in the product in the particle, average loading amount is the 12.0494g/ bag, and the assay sampling amount is 5g, and content is the 0.403mg/ bag.
Three, Tianjin * * pharmaceutcal corporation, Ltd flu * * particle (Sugarless type) in the detection of paracetamol
(1) high performance liquid chromatography-mass spectrometry carries out qualitative determination
Experimental technique is identical with method described in; Difference is: high performance liquid chromatogram-mass spectrometry moving phase water adopts the 30mmol/L ammonium acetate solution, and organic phase adopts methyl alcohol, is mobile phase A with the water; Organic phase is a Mobile phase B, and the gradient elution step is as shown in table 9; Mass spectrum condition impact energy adopts 16V.
Table 9, gradient elution step
(2) high performance liquid chromatography quantitative measurement
Experimental technique is identical with method described in, and difference is: use 60% methanol aqueous solution as extraction agent in the preparation of need testing solution, moving phase C is 0.2% phosphate aqueous solution; The gradient elution step is as shown in table 10.
Table 10, gradient elution step
Get 0709051 lot sample article, repeat 2 times, the result takes the mean.The result shows, 0709051 batch of flu of this manufacturer production * * detecting paracetamol in particle (Sugarless type) product, average loading amount is the 2.9601g/ bag, and the assay sampling amount is about 3g, and content is the 0.331mg/ bag, and average recovery is 99.2%.
Four, Hebei * * * pharmaceutcal corporation, Ltd flu * * particle in the detection of paracetamol
(1) high performance liquid chromatography-mass spectrometry carries out qualitative determination
Experimental technique is identical with method described in; Difference is: high performance liquid chromatogram-mass spectrometry moving phase water adopts the 25mmol/L ammonium acetate solution, and organic phase adopts methyl alcohol, is mobile phase A with the water; Organic phase is a Mobile phase B, and the gradient elution step is as shown in table 11; Mass spectrum condition impact energy adopts 20V.
Table 11, gradient elution step
(2) high performance liquid chromatography quantitative measurement
Experimental technique is identical with method described in, and difference is: use 65% methanol aqueous solution as extraction agent in the preparation of need testing solution, moving phase C is 0.5% phosphate aqueous solution; The gradient elution step is as shown in table 12.
Table 12, gradient elution step
Get 4 batches sample, get 2 samples for every batch, the result takes the mean.The result shows, detects paracetamol in four batches of products that this producer produced in 2007 to 2008, measures the result and sees table 13.
Table 13, Hebei * * * pharmaceutcal corporation, Ltd's flu * * particle in the testing result of paracetamol
Five, Jiangxi * * * pharmaceutcal corporation, Ltd flu * * particle in the detection of paracetamol
(1) high performance liquid chromatography-mass spectrometry carries out qualitative determination
Experimental technique is identical with method described in; Difference is: high performance liquid chromatogram-mass spectrometry moving phase water adopts the 15mmol/L ammonium acetate solution, and organic phase adopts methyl alcohol, is mobile phase A with the water; Organic phase is a Mobile phase B, and the gradient elution step is as shown in table 14; Mass spectrum condition impact energy adopts 14V.
Table 14, gradient elution step
(2) high performance liquid chromatography quantitative measurement
Experimental technique is identical with method described in, and difference is: use 55% methanol aqueous solution as extraction agent in the preparation of need testing solution, moving phase C is 0.4% phosphate aqueous solution; The gradient elution step is as shown in Tble 15.
Table 15, gradient elution step
Get 20080202 lot sample article, repeat 2 times, the result takes the mean.Detect paracetamol in 20080202 batches of products of this manufacturer production, average loading amount is the 12.1033g/ bag, and the assay sampling amount is about 5g, and content is the 0.101mg/ bag, and average recovery is 99.87%.
Claims (9)
1. the method for paracetamol in the detection composition; Comprise the steps: to carry out the discriminating and the structural identification of the paracetamol in the composition through monitoring following ion with high performance liquid chromatography-mass spectrometry method: parent ion 152.1, daughter ion 110.1 and daughter ion 93.1, carry out the assay of paracetamol with high performance liquid chromatography;
In said high performance liquid chromatography-mass spectrometry method, the water of the moving phase of employing is the 10-50mmol/L ammonium acetate solution, and organic phase is a methyl alcohol;
The water of the moving phase in the said high performance liquid chromatography is 0.1～0.5% phosphate aqueous solution for the quality percentage composition, and organic phase is a methyl alcohol.
2. method according to claim 1 is characterized in that: in said high performance liquid chromatography-mass spectrometry method, the water of the moving phase of employing is the 10mmol/L ammonium acetate solution.
3. method according to claim 1 and 2; It is characterized in that: carry out gradient elution with said moving phase in said high performance liquid chromatography-mass spectrometry method; The starting point of said moving phase is 95% volume water: 5% volume organic phase; The point of middle process comprises 20% volume water: 80% volume organic phase, terminal point are 95% volume water: 5% volume organic phase.
4. method according to claim 1 and 2 is characterized in that: in said high performance liquid chromatography-mass spectrometry method, and ion gun: electrospray ionization source; Scan pattern: reaction of high order monitoring; Polarity: kation; And impact energy: 10～20V.
5. method according to claim 1 and 2 is characterized in that: the water of the moving phase in the said high performance liquid chromatography is 0.1% phosphate aqueous solution.
6. method according to claim 1 and 2 is characterized in that: carry out gradient elution with said moving phase in the said high performance liquid chromatography, the volume ratio of water and organic phase is 89%～92%: 11%～8% in the starting point of said moving phase and the terminal point.
7. method according to claim 1 and 2; It is characterized in that: comprise the steps: to use volumn concentration said composition to be extracted in the said high performance liquid chromatography as the methanol solution of 50%-70%; Obtain extract, said extract is carried out said high performance liquid chromatography detect.
8. method according to claim 1 and 2 is characterized in that: said composition is the Chinese patent drug composition.
9. method according to claim 8 is characterized in that: said Chinese patent drug composition is type of curing cold Chinese patent drug composition or antirheumatic Chinese patent drug composition.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102519921A (en) * | 2011-11-14 | 2012-06-27 | 上海大学 | Method for measuring paracetamol by using CdTe nano fluorescent probe |
| CN107655993A (en) * | 2017-09-28 | 2018-02-02 | 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 paracetamol and other chemicalses in detection herbal beverage |
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2009
- 2009-05-11 CN CN2009100839487A patent/CN101566608B/en not_active Expired - Fee Related
Non-Patent Citations (5)
| Title |
|---|
| C.Celma et.al..Simultaneous determination of paracetamol and chlorpheniramine in human plasma by liquid chromatography-tandem mass spectrometry.《Journal of Chromatography A》.2000,第870卷77-86. * |
| 宁素云等.中成药中非法掺入对乙酰氨基酚的检测方法研究.《时珍国医国药》.2008,第19卷(第5期),1171-1172. * |
| 谭志荣等.高效液相色谱离子阱质谱联用法同时测定人血浆中曲马多和对乙酰氨基酚浓度.《药物分析杂志》.2005,第25卷(第7期),795-798. * |
| 赵永芳等.第九章高效液相色谱-流动相.《生物化学技术原理及应用》.2008,(第4版),151-152. * |
| 陈妙英等.固相萃取-高效液相色谱法测定人血浆中对乙酰氨基酚.《中国临床药学杂志》.2001,第10卷(第1期),17-19. * |
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