CN103913433A - Online detection method for double-effect concentration process of danhong injection - Google Patents
Online detection method for double-effect concentration process of danhong injection Download PDFInfo
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Abstract
The invention provides an online detection method for a double-effect concentration process of danhong injection. The method comprises the following steps: acquiring near infrared transmittance spectroscopy of danhong injection concentrate online by arranging a near infrared online detection device and collecting a concentrate sample; respectively measuring various pieces of quality control index information of the concentrate sample by a drying weighing method and high-performance liquid chromatography; removing abnormal spectrums; selecting a near infrared spectroscopy modeling waveband and a preprocessing method; establishing various quality control index quantitative models by a multivariate calibration algorithm; investigating the performance of the models by adopting various model evaluation indexes; online analyzing the variation trend of each quality control index in the concentration process by using the established models. According to the method, a near infrared online analysis technology is introduced into the concentration process of the danhong injection, so that the real-time monitoring of each quality control index (tanshinol, protocatechualdehyde, hydroxysafflor yellow A, rosmarinic acid, salvia acid B and moisture content) can be realized, the improvement on the quality control level in the danhong injection concentration process is facilitated, and the stable and reliable product quality is fully guaranteed.
Description
Technical field
The invention belongs near infrared online detection field, be specifically related to a kind of DANHONG ZHUSHEYE economic benefits and social benefits concentration process online test method.
Background technology
DANHONG ZHUSHEYE is the patent Chinese patent drug of first quick solution whole body internal organs blood supply insufficiency of China and ischemic Infraction, have promoting blood circulation and removing blood stasis, the function of promoting blood circulation, activating collaterals, the compound preparation being formed by the red sage root and safflower.That the red sage root has is promoting blood circulation and removing blood stasis, effect of regulating qi-flowing for relieving pain, is one of herbal species of widespread use clinically.From the red sage root, separate the water soluble ingredient obtaining and have danshensu, protocatechualdehyde and tanshin polyphenolic acid B etc.And safflower has effect promoting blood circulation and removing obstruction in channels, contain yellow and red two kinds of pigments, effective constituent mainly concentrates on water-soluble carthamin yellow, as hydroxyl radical carthamin yellow carthamus A etc.Concentration technology is the critical process link of DANHONG ZHUSHEYE production run, and its fundamental purpose is to make the effective constituent in extract obtain enrichment, is beneficial to refining purifying link of later stage.Traditional concentration process quality control mainly relies on operating personnel's the physical index such as experience or densitometer method of discrimination, time and effort consuming, and the impact of the effective constituent concentration change of having ignored system on product homogeneous, easily causes the unstable of different batches concentrate quality.Therefore the online test method of crucial quality control index in research and development DANHONG ZHUSHEYE economic benefits and social benefits concentration process, contribute to solve the quality Control of closing key control index in DANHONG ZHUSHEYE economic benefits and social benefits concentration process, there is Great significance for the progress of Chinese medicine industrial technology and product quality upgrading.
Near infrared (NIR) spectral technique is as a kind of green analytical technology of quick nondestructive, compared with conventional art, there is express-analysis, pollution-free, sample preparation simple, without consuming the features such as reagent.In recent years, near-infrared spectrum technique has more and more been applied to traditional Chinese medicine research, comprises the online examination and controlling of the discriminating of the medicinal material place of production, active principle assay and pharmacy procedure.It seems from Recent study progress, near-infrared spectral analysis technology is to be hopeful one of process analysis technique realizing at Chinese Traditional Medicine online detection and quality control most.In traditional Chinese medicine quality control and production application field, near infrared spectrum is applied to the existing Patents document of mensuration of index components as a kind of online measuring technique, as patent: in Chinese medicine production technology, product quality indicator detects (CN02137234.9) online, the method (CN200710022408.9) of near infrared spectrum quick online detection Chinese medicine Kuhuang injection effective ingredient, application process (CN200810050095.2) and a kind of method (CN200410090617.3) of Chinese medicine production technology being carried out in real time monitoring etc. of near infrared online detection technology in Chinese medicine YIQING KELI is produced.But these patents are off-line and gather near infrared spectrum, also institute's established model are not really applied to on-line analysis.
At present near infrared spectrum in detecting conventional method for establishing model more be principal component regression (PCR) and offset minimum binary (PLS).Wherein, the model that PLS sets up is more better than the model that PCR sets up, because in PLS, independent variable X and dependent variable Y data matrix are decomposed simultaneously, with respect to only independent variable X matrix being decomposed in PCR, not only eliminate the garbage in X and Y, and made independent variable X major component directly associated with analyzed component concentration Y, PLS method is better than PCR, has now become the method that enjoys high praise in Chemical Measurement.
Summary of the invention
The object of the present invention is to provide a kind of online test method of DANHONG ZHUSHEYE economic benefits and social benefits concentration process.The detection target of the method is to realize the on-line quantitative analysis of each quality control index in DANHONG ZHUSHEYE economic benefits and social benefits concentration process, is DANHONG ZHUSHEYE economic benefits and social benefits concentration process quality control supplying method.
The present invention is achieved through the following technical solutions:
1. design near infrared online detection device
Near infrared online detection device comprises the first valve (1), the second valve (2), the 3rd valve (3), the 4th valve (4), concentrator one is imitated heating chamber (5), concentrator one is imitated vaporization chamber (6), concentrator two is imitated heating chamber (5 '), concentrator two is imitated vaporization chamber (6 '), circulation house steward bypass (7), miniature magnetic driving gear pump (8), filtrator (9), flow cell (10), fibre-optical probe (11), stopple coupon (12), near infrared spectrometer (13), one effect circulation house steward (14), two effect circulation house steward (14 ') and steam pipeworks, concentrator one is imitated heating chamber (5) and is imitated vaporization chamber (6) by effect circulation house steward (14) connection concentrator one, concentrator two is imitated heating chamber (5 ') and is imitated vaporization chamber (6 ') by two effect circulation house stewards (14 ') connection concentrators two, concentrator one is imitated vaporization chamber (6) and is imitated heating chamber (5 ') by steam pipework (15) connection concentrator one, circulation house steward bypass (7) is connected to concentrator one with the branch road form that circulates and imitates heating chamber (5) and concentrator one to imitate the effect circulation house steward of one between vaporization chamber (6) (14) upper, the first valve (1), the second valve (2), miniature magnetic driving gear pump (8), filtrator (9), it is upper that flow cell (10) is connected to circulation house steward bypass (7) with series system, and flow cell (10) connects near infrared spectrometer (13), the 3rd valve (3) by fibre-optical probe (11), the 4th valve (4) and stopple coupon (12) series connection are also connected to circulation house steward bypass (7) above with branch road form, near flow cell (10).
2. online acquisition near-infrared transmission spectrum and concentrate sample
After concentrated beginning, open the first valve (1) and the second valve (2), communication loop pipeline (7), concentrate enters filtrator (9) by miniature magnetic driving gear pump (8), after filtering out impurities, arrive flow cell (10), the near infrared spectrum of concentrate near infrared spectrometer (13) online acquisition flow cell, when sampling, open the 3rd valve (3), solution to be concentrated is closed the 3rd valve (3) after being full of stopple coupon (12), open the 4th valve (4), collect concentrate sample and be used for measuring every quality control index, in flow cell (10) and circulation line, depositing in water flow velocity is controlled at 120 mL/min, filtrator is for most of solid impurity particle of filtering depositing in water liquid, filtering accuracy is 60 microns.
Adopt transmission beam method to gather near infrared spectrum, spectral range is 4500 cm
-1~ 12000 cm
-1, scanning times is 32 times, resolution is 8 cm
-1, take air as reference.
Spectrum and concentrate sample online acquisition are divided three phases: the first stage, the extract that the red sage root, flos carthami water extraction are obtained is successively introduced in an effect vaporization chamber (6) and two effect vaporization chambers (6 ') by vacuum, until tapping finishes, in process, every 5 minutes online acquisition near infrared spectrums, sampled from sample tap every 20 minutes; Subordinate phase, imitates the concentrate suction one in two effect vaporization chambers in vaporization chamber, in process, every 2.5 minutes online acquisition near infrared spectrums, samples from sample tap every 5 minutes; Phase III, concentrate is all transferred to after an effect vaporization chamber, and every 30 seconds online acquisition near infrared spectrums, every 2 minutes, from sample tap sampling, until liquid density reaches 1.27 ~ 1.28g/ml, concentration process finished.
3. adopt traditional analysis (high performance liquid chromatography and oven dry weight method) to record each quality control index information in concentrate sample
Each quality control index of described concentrate sample comprises danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid, tanshin polyphenolic acid B and water percentage, adopts high performance liquid chromatography (HPLC) to measure danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid and tanshin polyphenolic acid B in concentrate sample; Use and dry weight method mensuration water percentage.
(1) high performance liquid chromatography:
Condition: Agilent eclipse C18 analytical column (250
4.6 mm, 5 μ are m); Flow velocity 1 mL/min; 35 ℃ of column temperatures; Sample size 5 μ L; Mobile phase: A is methyl alcohol, and B is 0.5% aqueous formic acid (v/v), and gradient elution program is: 0 ~ 20 min, A:9% → 39%; 20 ~ 36 min, A:39% → 47%; 36 ~ 39 min, A:47% → 90%; 39 ~ 45 min, A:90%.Detect wavelength: 0 ~ 13 min, 280 nm(reference wavelength 360 nm); 13 ~ 21 min, 403 nm(reference wavelength 500 nm); 21 ~ 45 min, 280 nm(reference wavelength 360 nm);
Concentrate sample in 1500 r/min supercentrifuges centrifugal 10 minutes, then be diluted to different multiples, filter (0.45 μ m miillpore filter), get subsequent filtrate for liquid phase analysis.
Specification Curve of Increasing: precision takes danshensu respectively, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid and tanshin polyphenolic acid B reference substance are appropriate, use mobile phase (methyl alcohol-0.5% formic acid, v/v, 50:50) dilution, make single component reference substance storing solution, by storing solution proportional diluted, be made into the working fluid of variable concentrations, sample introduction analysis under above-mentioned chromatographic condition, with chromatographic peak area Y, sample introduction concentration X is carried out to linear regression, result shows, danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, the range of linearity of Rosmarinic acid and tanshin polyphenolic acid B is respectively 9.84 ~ 147.6, 1.13 ~ 22.68, 3.74 ~ 37.41, 4.83 ~ 57.98, 52.80 ~ 1056 μ g/mL, coefficient R value is all greater than 0.9998.
(2) dry weight method: weighedly dry measuring cup to constant weight (after twice oven dry, weight differential is less than 5 mg, note
x 0 ), measure 1 mL concentrate to flat bottle, weigh (
x 1 ), dry to constant weight in 105 ℃, take out and put cooling 30 min in exsiccator, weigh rapidly (
x 2 ), calculate water percentage by following formula:
4. rejecting abnormalities spectrum
In economic benefits and social benefits concentration process, due to acutely the rocking of equipment, easily cause the spectrum of flow cell collection to occur baseline wander or the situation such as burr is obvious, thereby cause the decline of model accuracy.The present invention calculates the mahalanobis distance of original near infrared spectrum, and uses Xiao Weile (Chauvenet) criterion rejecting abnormalities spectrum.If (the residual error Man Zu ∣ Vi ∣ > Wn σ of 1≤i≤n) Xi is regarded as abnormal data to measured value Xi, is rejected.Wherein, Vi is residual error, and σ is standard deviation, and Wn can table look-up and obtain.
5. select near infrared spectrum modeling wave band and preprocess method
Adopt first order derivative method, the filtering of Norris derivative, deduct straight line and standard normal variable converter technique to spectrum pre-service, for eliminating the impact near infrared spectrum such as baseline wander, noise, solid particle size, surface scattering and change in optical path length.The preprocessing procedures of danshensu, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid and tanshin polyphenolic acid B model comprises: first order derivative, standard normal variable conversion and Norris derivative filtering processing; The preprocessing procedures of protocatechualdehyde model comprises: first order derivative and deduct straight line; The preprocessing procedures of water percentage model comprises: first order derivative.
The modeling wave band of danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid, tanshin polyphenolic acid B and water percentage model is 5446.2 ~ 6101.9 cm
-1with 7498.2 ~ 9403.6 cm
-1.
6. use Multivariate Correction algorithm to set up each quality control index model, and adopt each model-evaluation index to investigate model performance;
Adopt partial least-squares regression method to set up each quality control index model.Model-evaluation index comprises: model-evaluation index comprises that related coefficient (R), calibration set root-mean-square error (RMSEC), calibration set verify root-mean-square error (RMSECV), calibration set relative deviation (RSEC) mutually, relatively analytical error (RPD).When R value is less than RMSECV value close to 1, RMSEC value, and both are as far as possible little, and RSEC is less than 20%, RPD >=3 o'clock, illustrate that institute's established model has good stability and precision of prediction, can be for the online detection of DANHONG ZHUSHEYE concentration process.
7. the variation tendency for the each quality control index of on-line analysis DANHONG ZHUSHEYE economic benefits and social benefits concentration process by established model
The near infrared light spectrogram of online acquisition DANHONG ZHUSHEYE economic benefits and social benefits concentrate, is input to spectroscopic data in calibration model, through calculating the information that can learn in real time each quality control index in concentrate.
Adopt partial least-squares regression method to set up each quality control index model.World model is that concentrate sample is classified not according to concentration, all for modeling; Partial model, for using principal component analytical method that concentrate sample is divided into two classes according to concentration height, is set up respectively the partial model of each quality control index according to classification.In the time that world model's performance is not good, can use partial model to improve model performance and predictive ability.
The present invention nearly infrared on line analysis technology is incorporated into the economic benefits and social benefits concentration process of DANHONG ZHUSHEYE, realize the Real-Time Monitoring to each quality control index (danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid, tanshin polyphenolic acid B and water percentage), be conducive to improve the quality control level of DANHONG ZHUSHEYE economic benefits and social benefits concentration process, fully guarantee constant product quality, reliable.
Accompanying drawing explanation
Fig. 1 is economic benefits and social benefits concentration process near infrared online detection system schematic.
Fig. 2 is concentrate sample relative density and water percentage correlationship figure.
Fig. 3 is economic benefits and social benefits concentration process danshensu predicted value and measured value comparison diagram while using world model.
Fig. 4 is economic benefits and social benefits concentration process protocatechualdehyde predicted value and measured value comparison diagram while using world model.
Fig. 5 is economic benefits and social benefits concentration process hydroxyl radical carthamin yellow carthamus A predicted value and measured value comparison diagram while using world model.
Fig. 6 is economic benefits and social benefits concentration process Rosmarinic acid predicted value and measured value comparison diagram while using world model.
Fig. 7 is economic benefits and social benefits concentration process tanshin polyphenolic acid B predicted value and measured value comparison diagram while using world model.
Fig. 8 is economic benefits and social benefits concentration process water percentage predicted value and measured value comparison diagram while using world model.
Fig. 9 is concentrate sample spectra principal component scores figure.
Figure 10 is economic benefits and social benefits concentration process danshensu predicted value and measured value comparison diagram while using partial model.
Figure 11 is economic benefits and social benefits concentration process protocatechualdehyde predicted value and measured value comparison diagram while using partial model.
Figure 12 is economic benefits and social benefits concentration process hydroxyl radical carthamin yellow carthamus A predicted value and measured value comparison diagram while using partial model.
Figure 13 is economic benefits and social benefits concentration process Rosmarinic acid predicted value and measured value comparison diagram while using partial model.
Figure 14 is economic benefits and social benefits concentration process tanshin polyphenolic acid B predicted value and measured value comparison diagram while using partial model.
Figure 15 is economic benefits and social benefits concentration process water percentage predicted value and measured value comparison diagram while using partial model.
Embodiment
Be described further below in conjunction with drawings and Examples.
Embodiment 1(uses whole concentrate Sample Establishing world model)
1. design near infrared online detection device
Referring to Fig. 1, near infrared online detection device comprises that the first valve 1, the second valve 2, the 3rd valve 3, the 4th valve 4, concentrator one imitate heating chamber 5, concentrator one and imitate that vaporization chamber 6, concentrator two are imitated heating chamber 5 ', concentrator two is imitated vaporization chamber 6 ', circulation house steward bypass 7, miniature magnetic driving gear pump 8, filtrator 9, flow cell 10, fibre-optical probe 11, stopple coupon 12, near infrared spectrometer 13, an effect circulation house steward 14, two effect circulation house steward 14 ' and steam pipeworks, concentrator one is imitated heating chamber 5 and is connected concentrator one by an effect circulation house steward 14 and imitate vaporization chamber 6, concentrator two is imitated heating chamber 5 ' and is imitated vaporization chamber 6 ' by two effect circulation house stewards 14 ' connection concentrators two, concentrator one is imitated vaporization chamber 6 and is connected concentrator one by steam pipework 15 and imitate heating chamber 5 ', circulation house steward bypass 7 is connected to concentrator one with circulation branch road form and imitates heating chamber 5 and concentrator one and imitate on the effect of one between vaporization chamber 6 circulation house steward 14, the first valve 1, the second valve 2, miniature magnetic driving gear pump 8, filtrator 9, flow cell 10 is connected in circulation house steward bypass 7 with series system, flow cell 10 connects near infrared spectrometer 13 by fibre-optical probe 11, the 3rd valve 3, the 4th valve 4 and stopple coupon 12 are connected and are connected in circulation house steward bypass 7 with branch road form, near flow cell 10.
2. the online acquisition of near infrared spectrum and concentrate sample
After concentrated beginning, open the first valve 1 and the second valve 2, communication loop pipeline 7, concentrate enters filtrator 9 by miniature magnetic driving gear pump 8, arrives flow cell 10 after filtering out impurities, the near infrared spectrum of concentrate near infrared spectrometer 13 online acquisition flow cells, when sampling, open the 3rd valve 3, solution to be concentrated is closed the 3rd valve 3 after being full of stopple coupon 12, open the 4th valve 4, collect concentrate sample and be used for measuring every quality control index.In flow cell 10 and circulation line, depositing in water flow velocity is controlled at 120 mL/min, and filtrator is for most of solid impurity particle of filtering depositing in water liquid, and filtering accuracy is 60 microns.
Adopt transmission beam method to gather near infrared spectrum, spectral range is 4500 cm
-1~ 12000 cm
-1, scanning times is 32 times, resolution is 8 cm
-1, take air as reference.Spectrum and concentrate sample online acquisition are divided three phases: the first stage, the extract that the red sage root, flos carthami water extraction are obtained is successively introduced in an effect vaporization chamber 6 and two effect vaporization chambers 6 ' by vacuum, until tapping finishes, in process, every 5 minutes online acquisition near infrared spectrums, sampled from sample tap every 20 minutes; Subordinate phase, imitates the concentrate suction one in two effect vaporization chambers 6 ' in vaporization chamber 6, in process, every 2.5 minutes online acquisition near infrared spectrums, samples from sample tap every 5 minutes; Phase III, concentrate is all transferred to after an effect vaporization chamber 6, and every 30 seconds online acquisition near infrared spectrums, every 2 minutes, from sample tap sampling, until liquid density reaches 1.27 ~ 1.28g/ml, concentration process finished.
Collect the concentrate sample in different batches economic benefits and social benefits concentration process, random wherein 2 batch datas of selecting collect as checking, and all the other samples participate in modeling as calibration set.Repeat the concentrated experiment of 10 batches of DANHONG ZHUSHEYEs, the experiment of every batch all samples and gathers spectrum in the same manner.Obtain altogether 176 concentrate samples.
3. each quality control index is measured
Each quality control index comprises danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid, tanshin polyphenolic acid B and water percentage.Adopt high performance liquid chromatography (HPLC) to measure danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid and tanshin polyphenolic acid B in concentrate sample; Use and dry weight method mensuration water percentage.
(1) high performance liquid chromatography: condition: Agilent eclipse C18 analytical column (250
4.6 mm, 5 μ are m); Flow velocity 1 mL/min; 35 ℃ of column temperatures; Sample size 5 μ L; Mobile phase: A is methyl alcohol, and B is 0.5% aqueous formic acid (v/v), and gradient elution program is: 0 ~ 20 min, A:9% → 39%; 20 ~ 36 min, A:39% → 47%; 36 ~ 39 min, A:47% → 90%; 39 ~ 45 min, A:90%.Detect wavelength: 0 ~ 13 min, 280 nm(reference wavelength 360 nm); 13 ~ 21 min, 403 nm(reference wavelength 500 nm); 21 ~ 45 min, 280 nm(reference wavelength 360 nm).
Concentrate sample in 1500 r/min supercentrifuges centrifugal 10 minutes, then be diluted to different multiples, filter (0.45 μ m miillpore filter), get subsequent filtrate for liquid phase analysis.
Specification Curve of Increasing: it is appropriate that precision takes danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid and tanshin polyphenolic acid B reference substance respectively, use mobile phase (methyl alcohol-0.5% formic acid, v/v, 50:50) dilution, make single component reference substance storing solution, by storing solution proportional diluted, be made into the working fluid of variable concentrations, sample introduction analysis under above-mentioned chromatographic condition.With chromatographic peak area Y, sample introduction concentration X is carried out to linear regression.Result shows, the range of linearity of danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid and tanshin polyphenolic acid B is respectively 9.84 ~ 147.6,1.13 ~ 22.68,3.74 ~ 37.41,4.83 ~ 57.98,52.80 ~ 1056 μ g/mL, coefficient R value is all greater than 0.9998.
(2) dry weight method: weighedly dry measuring cup to constant weight (after twice oven dry, weight differential is less than 5 mg, note
x 0 ), measure 1 mL concentrate to flat bottle, weigh (
x 1 ), dry to constant weight in 105 ℃, take out and put cooling 30 min in exsiccator, weigh rapidly (
x 2 ), calculate water percentage by following formula:
4. set up relative density-water percentage canonical plotting
Choose the sample of different densities in 8 economic benefits and social benefits concentration processs, measure water percentage simultaneously, take density as ordinate, water percentage is horizontal ordinate Criterion curve, and the fit equation obtaining is:
y=-0.005x+ 1.48,
r 2 =0.9972.From above-mentioned equation, between relative density and water percentage, there is good correlativity.In actual production process, can draw rapidly by water percentage the relative density of sample, the results are shown in Figure 2.
5. rejecting abnormalities spectrum
In economic benefits and social benefits concentration process, due to acutely the rocking of equipment, easily cause the spectrum of flow cell collection to occur baseline wander or the situation such as burr is obvious, thereby cause the decline of model accuracy.The present invention calculates the mahalanobis distance of spectrum, and uses Xiao Weile (Chauvenet) criterion rejecting abnormalities spectrum.If (the residual error Man Zu ∣ Vi ∣ > Wn σ of 1≤i≤n) Xi is regarded as abnormal data to measured value Xi, is rejected.Wherein, Vi is residual error, and σ is standard deviation, and Wn can table look-up and obtain.According to result of calculation, there is the spectral singularity of 17 samples, after these samples are rejected, remaining data is used for setting up quantitative model.
6. select near infrared spectrum modeling wave band and preprocess method
Adopt first order derivative method, the filtering of Norris derivative, deduct straight line and standard normal variable converter technique to spectrum pre-service, for eliminating the impact near infrared spectrum such as baseline wander, noise, solid particle size, surface scattering and change in optical path length.By different pretreatments method relatively on the impact of quality control index after, finally determine that the preprocessing procedures of danshensu, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid and tanshin polyphenolic acid B model comprises: first order derivative, standard normal variable conversion and Norris derivative filtering processing; The preprocessing procedures of protocatechualdehyde model comprises: first order derivative and deduct straight line; The preprocessing procedures of water percentage model comprises: first order derivative.
Wave band below need getting rid of in the time selecting modeling wave band: 4500 ~ 5445 cm
-1with 7500 ~ 12000 cm
-1wave band, two " water peak ".By the combined crosswise test of wave band, the modeling wave band of determining danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid, tanshin polyphenolic acid B and water percentage model is 5446.2 ~ 6101.9 cm
-1with 7498.2 ~ 9403.6 cm
-1.
7. adopt partial least-squares regression method to set up each quality control index overall situation quantitative correction model
Near infrared spectrum data after pretreatment, adopts least square regression to set up the overall quantitative correction model of danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid, tanshin polyphenolic acid B and water percentage, and model tuning result is referring to table 1.As can be seen from the table, the related coefficient of all index components is all greater than 0.98, and calibration set relative deviation is all less than 10%.Document shows that calibration model RPD value is greater than 3 and thinks institute's established model ideal, herein the RPD value of positive model for school building be all greater than 7, illustrate that to a certain extent the stability of model is better, be applicable to actual production process and detect online.
8. each quality control index variation tendency in on-line analysis economic benefits and social benefits concentration process
Suo Jian world model, for on-line analysis 1 batch of DANHONG ZHUSHEYE economic benefits and social benefits concentration process danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid, tanshin polyphenolic acid B concentration and water percentage, is predicted the outcome as shown in Fig. 3 ~ 8.As can be seen from the figure, the anticipation trend of each quality control index and the variation tendency of measured value are basically identical.Its RMSEP and RSEP value are referring to table 2, and RSEP is all controlled in 10%, meets the accuracy requirement of Chinese Traditional Medicine real-time analysis completely, illustrate that Liao Suojian world model has higher prediction accuracy.
Embodiment 2:
According to the method for embodiment 1, difference part is to use principal component analytical method to be divided into high-concentration and low-concentration two classes to concentrate sample, sets up respectively the partial model of each quality control index according to classification.
1. spectrum principal component analysis (PCA)
Collect 176 concentrate samples are carried out to principal component analysis (PCA), referring to figure, it is higher that the first principal component of high density sample obtains score value, and the first principal component value of low-density sample is lower, obtain score value 0.3 as boundary take first principal component, high-concentration and low-concentration (density) sample is divided into two classes.The above results shows, the sample larger to concentration span, and segmentation modeling may obtain more excellent predictive ability than global modeling.
2. adopt partial least-squares regression method to set up each quality control index Local Quantitative calibration model
From Fig. 3 ~ 8, can find out, because sample concentration scope is excessive, institute's quantitative model of building is in low concentration region prediction effect higher concentration area difference.Therefore, for principal component analysis (PCA) result, to low concentration group concentrate sample and the separately modeling again of high concentration group concentrate sample.The Local Quantitative model performance parameter evaluation of each quality control index is referring to table 3.Owing to easily causing model over-fitting because subnumber is too high, reduce on the contrary the estimated performance of model entirety.As can be seen from Table 3, choose low concentration region and independently set up after quantitative correction model, all being reduced largely because of subnumber of target component.Like this performance that makes model is further promoted.
3. partial correction model is predicted unknown sample
By built partial model for analyzing the concentration change with 1 batch of economic benefits and social benefits concentration process sample 6 special quality control index, its middle and high concentration sample pattern is for predicting the high concentration sample of economic benefits and social benefits concentration process, low concentration model is used for predicting low concentration sample, predict the outcome referring to Figure 10 ~ 15, its RMSEP and RSEP are referring to table 4.Except protocatechualdehyde and water percentage, the prediction effect of all the other 4 special quality control indexs is all improved largely.The undesirable possible cause of prediction effect of protocatechualdehyde is because its concentration in system is too low, is easily disturbed by the content information of other compositions, thereby affects the prediction accuracy of model.The result of this experiment shows, if the concentration range of sample is larger, takes local segmentation modeling that the predictive ability that makes model is obtained to lifting by a relatively large margin.Meanwhile, can infer from the modeling result of protocatechualdehyde, due near infrared spectrum self limitation (detectability >0.1%), the low concentration composition in complex matrices exists the not enough danger of prediction.
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Claims (4)
1. a DANHONG ZHUSHEYE economic benefits and social benefits concentration process online test method, is characterized in that, realizes by following steps:
(1) design near infrared online detection device
This device comprises the first valve (1), the second valve (2), the 3rd valve (3), the 4th valve (4), concentrator one is imitated heating chamber (5), concentrator one is imitated vaporization chamber (6), concentrator two is imitated heating chamber (5 '), concentrator two is imitated vaporization chamber (6 '), circulation house steward bypass (7), miniature magnetic driving gear pump (8), filtrator (9), flow cell (10), fibre-optical probe (11), stopple coupon (12), near infrared spectrometer (13), one effect circulation house steward (14), two effect circulation house steward (14 ') and steam pipeworks, concentrator one is imitated heating chamber (5) and is imitated vaporization chamber (6) by effect circulation house steward (14) connection concentrator one, concentrator two is imitated heating chamber (5 ') and is imitated vaporization chamber (6 ') by two effect circulation house stewards (14 ') connection concentrators two, concentrator one is imitated vaporization chamber (6) and is imitated heating chamber (5 ') by steam pipework (15) connection concentrator one, circulation house steward bypass (7) is connected to concentrator one with the branch road form that circulates and imitates heating chamber (5) and concentrator one to imitate the effect circulation house steward of one between vaporization chamber (6) (14) upper, the first valve (1), the second valve (2), miniature magnetic driving gear pump (8), filtrator (9), it is upper that flow cell (10) is connected to circulation house steward bypass (7) with series system, and flow cell (10) connects near infrared spectrometer (13), the 3rd valve (3) by fibre-optical probe (11), the 4th valve (4) and stopple coupon (12) series connection are also connected to circulation house steward bypass (7) above with branch road form, near flow cell (10),
(2) online acquisition near-infrared transmission spectrum and concentrate sample
After concentrated beginning, open the first valve (1) and the second valve (2), communication loop pipeline (7), concentrate enters filtrator (9) by miniature magnetic driving gear pump (8), after filtering out impurities, arrive flow cell (10), the near infrared spectrum of concentrate near infrared spectrometer (13) online acquisition flow cell, when sampling, open the 3rd valve (3), solution to be concentrated is closed the 3rd valve (3) after being full of stopple coupon (12), open the 4th valve (4), collect concentrate sample and be used for measuring every quality control index, in flow cell (10) and circulation line, depositing in water flow velocity is controlled at 120 mL/min, filtering accuracy is 60 microns,
Wherein near infrared spectral range is 4500 cm
-1~ 12000 cm
-1, scanning times is 32 times, resolution is 8 cm
-1, take air as reference;
(3) detect each quality control index in concentrate sample: quality control index is danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid, tanshin polyphenolic acid B and water percentage,
(a) adopt high effective liquid chromatography for measuring danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid and tanshin polyphenolic acid B; Concentrate sample in 1500 r/min supercentrifuges centrifugal 10 minutes, then be diluted to different multiples, 0.45 μ m filtering with microporous membrane, gets subsequent filtrate for liquid phase analysis;
Chromatographic condition: Agilent eclipse C18 analytical column, 250
4.6 mm, 5 μ m; Flow velocity 1 mL/min; 35 ℃ of column temperatures; Sample size 5 μ L; Mobile phase: A is methyl alcohol, and B is 0.5% aqueous formic acid (v/v), and gradient elution program is: 0 ~ 20 min, A:9% → 39%; 20 ~ 36 min, A:39% → 47%; 36 ~ 39 min, A:47% → 90%; 39 ~ 45 min, A:90%; Detect wavelength: 0 ~ 13 min, 280 nm; 13 ~ 21 min, 403 nm; 21 ~ 45 min, 280 nm;
(b) dry weight method and measure water percentage: weighed measuring cup of drying to constant weight, after twice oven dry, weight differential is less than 5 mg, note
x 0 , measure 1 mL concentrate to flat bottle, weigh (
x 1 ), dry to constant weight in 105 ℃, take out and put cooling 30 min in exsiccator, weigh rapidly (
x 2 ), calculate water percentage by following formula:
；
(4) rejecting abnormalities spectrum:
Calculate the mahalanobis distance of original near infrared spectrum, and use Xiao Weile criterion rejecting abnormalities spectrum, if (the residual error Man Zu ∣ Vi ∣ > Wn σ of 1≤i≤n) Xi is regarded as abnormal data to measured value Xi, rejected, wherein, Vi is residual error, and σ is standard deviation, and Wn can table look-up and obtain;
(5) select near infrared spectrum modeling wave band and preprocess method:
Adopt first order derivative method, the filtering of Norris derivative, deduct straight line and standard normal variable converter technique to spectrum pre-service, for eliminating the impact near infrared spectrum such as baseline wander, noise, solid particle size, surface scattering and change in optical path length, the preprocessing procedures of danshensu, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid and tanshin polyphenolic acid B model is: first order derivative, standard normal variable conversion and Norris derivative filtering processing; The preprocessing procedures of protocatechualdehyde model is: first order derivative and deduct straight line; The preprocessing procedures of water percentage model is: first order derivative;
The modeling wave band of danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid, tanshin polyphenolic acid B and water percentage model is 5446.2 ~ 6101.9 cm
-1with 7498.2 ~ 9403.6 cm
-1;
(6) use Multivariate Correction algorithm to set up each quality control index model, and adopt each model-evaluation index to investigate model performance:
Adopt partial least-squares regression method to set up each quality control index model, model-evaluation index comprises: model-evaluation index comprises that related coefficient (R), calibration set root-mean-square error (RMSEC), calibration set verify root-mean-square error (RMSECV), calibration set relative deviation (RSEC) mutually, analytical error (RPD) relatively, when R value is close to 1, RMSEC value is less than RMSECV value, and both are as far as possible little, RSEC is less than 20%, RPD >=3 o'clock, stability and precision of prediction that institute's established model has had are described, can be used for the online detection of DANHONG ZHUSHEYE concentration process;
(7) variation tendency for the each quality control index of on-line analysis DANHONG ZHUSHEYE economic benefits and social benefits concentration process by established model:
The near infrared light spectrogram of online acquisition DANHONG ZHUSHEYE concentrate, is input to spectroscopic data in calibration model, through calculating the information of learning in real time each quality control index in concentrate.
2. a kind of DANHONG ZHUSHEYE economic benefits and social benefits concentration process online test method according to claim 1, it is characterized in that, described spectrum and the concentrate sample online acquisition of step (2) divided three phases: the first stage, the extract that the red sage root, flos carthami water extraction are obtained is successively introduced in an effect vaporization chamber (6) and two effect vaporization chambers (6 ') by vacuum, until tapping finishes, in process, every 5 minutes online acquisition near infrared spectrums, sampled from sample tap every 20 minutes; Subordinate phase, imitates the concentrate suction one in two effect vaporization chambers (6 ') in vaporization chamber (6), in process, every 2.5 minutes online acquisition near infrared spectrums, samples from sample tap every 5 minutes; Phase III, concentrate is all transferred to after an effect vaporization chamber (6), and every 30 seconds online acquisition near infrared spectrums, every 2 minutes, from sample tap sampling, until liquid density reaches 1.27 ~ 1.28g/ml, concentration process finished.
3. a kind of DANHONG ZHUSHEYE economic benefits and social benefits concentration process online test method according to claim 1, it is characterized in that, step (a) Plays Drawing of Curve: take respectively danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, Rosmarinic acid and tanshin polyphenolic acid B reference substance, use methyl alcohol-0.5% formic acid, v/v, the mobile phase dilution of 50:50, make single component reference substance storing solution, by storing solution proportional diluted, be made into the working fluid of variable concentrations, sample introduction analysis under above-mentioned chromatographic condition, with chromatographic peak area Y, sample introduction concentration X is carried out to linear regression, record danshensu, protocatechualdehyde, hydroxyl radical carthamin yellow carthamus A, the range of linearity of Rosmarinic acid and tanshin polyphenolic acid B is respectively 9.84 ~ 147.6, 1.13 ~ 22.68, 3.74 ~ 37.41, 4.83 ~ 57.98, 52.80 ~ 1056 μ g/mL, coefficient R value is all greater than 0.9998.
4. require described a kind of DANHONG ZHUSHEYE economic benefits and social benefits concentration process online test method according to right 1, it is characterized in that: step (6) adopts partial least-squares regression method to set up each quality control index model, world model is that concentrate sample is classified not according to concentration, all for modeling, partial model is for using principal component analytical method that concentrate sample is divided into two classes according to concentration height, set up respectively the partial model of each quality control index according to classification, in the time that world model's performance is not good, can use partial model to improve model performance and predictive ability.
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