CN103913433B - 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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- Investigating Or Analysing Materials By Optical Means (AREA)
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 is and in particular to a kind of DANHONG ZHUSHEYE economic benefits and social benefits concentration process is examined online
Survey method.
Background technology
DANHONG ZHUSHEYE is the quick patent solving whole body internal organs blood supply insufficiency and ischemia Infraction of first, China
Chinese patent medicine, has blood circulation promoting and blood stasis dispelling, the function of TONGMAI SHULUO, the compound preparation being made up of Radix Salviae Miltiorrhizae Flos Carthami.Radix Salviae Miltiorrhizae has promoting blood circulation
Blood stasis dispelling, effect of regulating QI to relieve pain, are clinically one of wide variety of herbal species.Separate the water solublity obtaining to become from Radix Salviae Miltiorrhizae
Dividing has danshensu, protocatechualdehyde and salvianolic acid b etc..And Flos Carthami has functions that promoting blood circulation to remove obstruction in the collateral, containing yellow and red two kinds of colors
Element, effective ingredient is concentrated mainly on water solublity Carthamus yellow, such as Hydroxy Carthamus yellow a etc..Concentration technology is DANHONG injection
The critical process link of liquid production process, its main purpose is so that the effective ingredient in extracting solution is enriched with, and is beneficial to the later stage
Polishing purification link.Traditional concentration process quality control mainly relies on the physical indexs such as experience or the densimeter of operator to be sentenced
Other method, time and effort consuming, have ignored the impact homogeneous to product of the effective ingredient concentration change of system, easily cause different batches dense
Contracting liquid quality unstable.Therefore in research and development DANHONG ZHUSHEYE economic benefits and social benefits concentration process crucial quality control index on-line checking side
Method, contributes to solving the quality Control of crucial Con trolling index in DANHONG ZHUSHEYE economic benefits and social benefits concentration process, for Chinese medicine industry
Technological progress and product quality upgrading have Great significance.
Near-infrared (nir) spectral technique, as a kind of green analytical technology of quick nondestructive, compared with conventional art, has
Quick analysis, pollution-free, sample treatment is simple, the features such as need not consume reagent.In recent years, near-infrared spectrum technique is more next
More is applied to Chinese medicine research, including the on-line checking of medical material identification of habitats, active component assay and pharmacy procedure
And monitoring.From Recent study progress, near-infrared spectral analysis technology is to be hopeful most in Chinese Traditional Medicine in fact
One of process analysis technique of existing on-line checking and quality control.In Chinese medicine quality control and production application field, near infrared light
Spectrum is applied to the existing Patents documents of mensure of index components, such as patent: Chinese medicine produces work as a kind of online measuring technique
Product quality indicator on-line checking (cn02137234.9) in skill, near infrared spectrum quick online detection Chinese medicine Kuhuang injection has
The method (cn200710022408.9) of effect composition, application side in the production of Chinese medicine YIQING KELI for the near infrared online detection technology
Method (cn200810050095.2) and a kind of method (cn200410090617.3) that Chinese medicine production technology is carried out with monitor in real time
Deng.But these patents are offline collection near infrared spectrum, also institute's established model are not really applied to on-line analyses.
What at present near infrared spectrum detection, conventional method for establishing model was more is principal component regression (pcr) and minimum partially
Two take advantage of (pls).Wherein, pls set up model be better than pcr set up model because in pls, simultaneously to independent variable x and because
Variable y data matrix is decomposed, and only independent variable x matrix is decomposed with respect in pcr, not only eliminates the nothing in x and y
With information, and independent variable x main constituent is made directly to associate with analyzed constituent content y, pls method is better than pcr, becoming
Learn the method enjoying high praise in meterological.
Content of the invention
It is an object of the invention to provide a kind of online test method of DANHONG ZHUSHEYE economic benefits and social benefits concentration process.The method
Detection target is to realize the on-line quantitative analysis of each quality control index in DANHONG ZHUSHEYE economic benefits and social benefits concentration process, is that DANHONG ZHUSHEYE is double
Effect concentration process quality control provides method.
The present invention is to be achieved through the following technical solutions:
1. design near infrared online detection device
Near infrared online detection device includes the first valve (1), the second valve (2), the 3rd valve (3), the 4th valve
(4), concentrator one effect heating chamber (5), concentrator one effect vaporization chamber (6), concentrator two effect heating chamber (5 '), concentration set
Standby two effects vaporization chamber (6 '), circulation house steward's bypass (7), miniature magnetic driving gear pump (8), filter (9), flow cell (10),
Fibre-optical probe (11), probe tube (12), near infrared spectrometer (13), one effect circulation house steward (14), two effect circulation house steward (14 ') and
Steam pipework, concentrator one effect heating chamber (5) passes through effect circulation house steward (14) connection concentrator one imitates vaporization chamber (6),
Concentrator two effect heating chamber (5 ') passes through two effect circulation house steward (14 ') connection concentrators two imitates vaporization chamber (6 '), and concentration sets
Standby effect vaporization chamber (6) connects concentrator one by steam pipework (15) and imitates heating chamber (5 '), and circulation house steward's bypass (7) is to follow
The effect circulation that ring branch road form is connected between concentrator one effect heating chamber (5) and concentrator one effect vaporization chamber (6) is total
Pipe (14) on, the first valve (1), the second valve (2), miniature magnetic driving gear pump (8), filter (9), flow cell (10) with
Series system is connected in circulation house steward's bypass (7), and flow cell (10) connects near infrared spectrometer by fibre-optical probe (11)
(13), the 3rd valve (3), the 4th valve (4) and probe tube (12) are connected and are connected to circulation house steward's bypass (7) with branch road form
On, near flow cell (10).
2. online acquisition NIR transmittance spectroscopy and concentrated solution sample
After concentration starts, open the first valve (1) and the second valve (2), communication loop pipeline (7), concentrated solution passes through micro-
Type gear pump driven by magnetic force (8) enters filter (9), reaches flow cell (10), near infrared spectrometer (13) exists after filtering impurity
Line gathers the near infrared spectrum of concentrated solution in flow cell, during sampling, opens the 3rd valve (3), and solution to be concentrated is full of probe tube
(12) close the 3rd valve (3) afterwards, open the 4th valve (4), collect concentrated solution sample and be used for measuring every quality control index, circulation
In pond (10) and circulation line, water precipitating flow velocity controls in 120 ml/min, and the major part that filter is used for filtering in water precipitating liquid is solid
Body impurity particle, filtering accuracy is 60 microns.
Near infrared spectrum is gathered using transmission beam method, spectral region is 4500 cm-1~12000 cm-1, scanning times are 32
Secondary, resolution is 8 cm-1, with air as reference.
Spectrum and concentrated solution sample online acquisition divide three phases: the first stage, Radix Salviae Miltiorrhizae, flos carthami water extraction are obtained
Extracting solution is successively introduced into effect vaporization chamber (6) and two by vacuum and imitates in vaporization chamber (6 '), terminates up to tapping, during every
5 minutes online acquisition near infrared spectrums, every 20 minutes from sample tap sampling；Second stage, two is imitated the concentration in vaporization chamber
In liquid suction one effect vaporization chamber, during every 2.5 minutes online acquisition near infrared spectrums, every 5 minutes from sample tap sampling；
Phase III, after concentrated solution is fully transferred to an effect vaporization chamber, every 30 seconds online acquisition near infrared spectrums, at intervals of two minutes from
Sample tap samples, until medicinal liquid density reaches 1.27 ~ 1.28g/ml, concentration process terminates.
3. record each Quality Control in concentrated solution sample using traditional analysis (high performance liquid chromatography and weighting method after dried)
Indication information
Each quality control index of described concentrated solution sample include danshensu, protocatechualdehyde, Hydroxy Carthamus yellow a, fan change
Fragrant acid, salvianolic acid b and moisture content, using high performance liquid chromatography (hplc) measure danshensu in concentrated solution sample, protocatechualdehyde,
Hydroxy Carthamus yellow a, rosmarinic acid and salvianolic acid b；Measure moisture content using weighting method after dried.
(1) high performance liquid chromatography:
Condition: agilent eclipse c18 analytical column (2504.6 mm, 5 μm)；Flow velocity 1 ml/min；Column temperature
35 ℃；Sample size 5 μ l；Mobile phase: a is methanol, 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%.Detection
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)；
Concentrated solution sample is centrifuged 10 minutes in 1500 r/min high speed centrifuges, then is diluted to different multiples, filtration
(0.45 m microporous filter membrane), takes subsequent filtrate to be used for liquid phase analysis.
Specification Curve of Increasing: precision weighs danshensu, protocatechualdehyde, Hydroxy Carthamus yellow a, rosmarinic acid and pellet respectively
Phenolic acid b reference substance is appropriate, using mobile phase (methanol -0.5% formic acid, v/v, 50:50) dilution, makes the storage of single component reference substance
Standby liquid, storing solution proportional diluted is made into the working solution of variable concentrations, and sample introduction analysis under above-mentioned chromatographic condition, with chromatographic peak
Area y carries out linear regression to sample introduction concentration x, and result shows, danshensu, protocatechualdehyde, Hydroxy Carthamus yellow a, Herba Rosmarini Officinalis
Acid and salvianolic acid b the range of linearity be respectively 9.84 ~ 147.6,1.13 ~ 22.68,3.74 ~ 37.41,4.83 ~ 57.98,52.80 ~
1056 μ g/ml, correlation coefficient r value is all higher than 0.9998.
(2) weighting method after dried: (after drying twice, weight differential is less than 5 mg, note to the weighing botle of weighed drying to constant weightx 0 ), measure 1 ml concentrated solution to flat bottle, weigh (x 1 ), dry to constant weight in 105 DEG C, take out and put cooling 30 in exsiccator
Min, weigh rapidly (x 2 ), moisture content according to the following formula:
4. rejecting abnormalities spectrum
Acutely rocking due to equipment in economic benefits and social benefits concentration process, baseline drift in the spectrum being easily caused flow cell collection
Or burr obvious situations such as, thus causing the decline of model accuracy.The present invention calculates the mahalanobis distance of original near infrared spectrum, and
Using Xiao Weile (chauvenet) criterion rejecting abnormalities spectrum.If the residual error of measured value xi (1≤i≤n) meets vi ＞ wn σ
Then xi is considered abnormal data, 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
Using First derivative spectrograply, the filtering of norris derivative, deduct straight line and standard normal variable converter technique to spectrum
Pretreatment, for eliminating baseline drift, noise, solid particle size, surface scattering and change in optical path length etc. near infrared spectrum
Impact.Danshensu, the preprocessing procedures of Hydroxy Carthamus yellow a, rosmarinic acid and salvianolic acid b model include: single order is led
Number, standard normal variable conversion and norris derivative Filtering Processing；The preprocessing procedures of protocatechualdehyde model include: single order
Derivative and deduct straight line；The preprocessing procedures of moisture content model include: first derivative.
Danshensu, protocatechualdehyde, Hydroxy Carthamus yellow a, the modeling ripple of rosmarinic acid, salvianolic acid b and moisture content model
Section is 5446.2 ~ 6101.9 cm-1With 7498.2 ~ 9403.6 cm-1.
6. set up each quality control index model using Multivariate Correction algorithm, and model is investigated using each model-evaluation index
Energy；
Each quality control index model is set up using partial least-squares regression method.Model-evaluation index includes: model-evaluation index
Root-mean-square error (rmsecv), correction are mutually authenticated including correlation coefficient (r), calibration set root-mean-square error (rmsec), calibration set
Collection relative deviation (rsec), relation analysis error (rpd).When r value is less than rmsecv value close to 1, rmsec value, and both are to the greatest extent
May be little, when rsec is less than 20%, rpd >=3, illustrates that institute's established model has preferable stability and precision of prediction, can be used for pellet
The on-line checking of red injection concentration process.
7. established model is used for the variation tendency of each quality control index in on-line analyses DANHONG ZHUSHEYE economic benefits and social benefits concentration process
The atlas of near infrared spectra of online acquisition DANHONG ZHUSHEYE economic benefits and social benefits concentrated solution, spectroscopic data is input to calibration model
In, through calculating the information that can learn each quality control index in concentrated solution in real time.
Each quality control index model is set up using partial least-squares regression method.World model is not divided by concentration for concentrated solution sample
Class, is completely used for modeling；Partial model is, using principal component analytical method, according to concentration level, concentrated solution sample is divided into two classes,
Set up the partial model of each quality control index according to classification respectively.When world model's performance is not good, can be carried using partial model
High 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, realizes to each Quality Control
The real-time monitoring of index (danshensu, protocatechualdehyde, Hydroxy Carthamus yellow a, rosmarinic acid, salvianolic acid b and moisture content), favorably
In the quality control level improving DANHONG ZHUSHEYE economic benefits and social benefits concentration process, fully ensure that product quality is stable, reliable.
Brief description
Fig. 1 is economic benefits and social benefits concentration process near infrared online detection system schematic.
Fig. 2 is concentrated solution sample relative density and moisture content dependency relation figure.
Fig. 3 is using economic benefits and social benefits concentration process danshensu predictive value during world model and measured value comparison diagram.
Fig. 4 is using economic benefits and social benefits concentration process protocatechualdehyde predictive value during world model and measured value comparison diagram.
Fig. 5 is using economic benefits and social benefits concentration process Hydroxy Carthamus yellow a predictive value during world model and measured value comparison diagram.
Fig. 6 is using economic benefits and social benefits concentration process rosmarinic acid predictive value during world model and measured value comparison diagram.
Fig. 7 is using economic benefits and social benefits concentration process salvianolic acid b predictive value during world model and measured value comparison diagram.
Fig. 8 is using economic benefits and social benefits concentration process hydrated comples ion value during world model and measured value comparison diagram.
Fig. 9 is concentrated solution sample spectra principal component scores figure.
Figure 10 is using economic benefits and social benefits concentration process danshensu predictive value during partial model and measured value comparison diagram.
Figure 11 is using economic benefits and social benefits concentration process protocatechualdehyde predictive value during partial model and measured value comparison diagram.
Figure 12 is using economic benefits and social benefits concentration process Hydroxy Carthamus yellow a predictive value during partial model and measured value comparison diagram.
Figure 13 is using economic benefits and social benefits concentration process rosmarinic acid predictive value during partial model and measured value comparison diagram.
Figure 14 is using economic benefits and social benefits concentration process salvianolic acid b predictive value during partial model and measured value comparison diagram.
Figure 15 is using economic benefits and social benefits concentration process hydrated comples ion value during partial model and measured value comparison diagram.
Specific embodiment
It is described further with reference to the accompanying drawings and examples.
Embodiment 1(uses whole concentrated solution Sample Establishing world models)
1. design near infrared online detection device
Referring to Fig. 1, near infrared online detection device includes the first valve 1, the second valve 2, the 3rd valve 3, the 4th valve
4th, concentrator one effect heating chamber 5, concentrator one effect vaporization chamber 6, concentrator two effect heating chamber 5 ', concentrator two effect are steamed
Send out room 6 ', circulation house steward's bypass 7, miniature magnetic driving gear pump 8, filter 9, flow cell 10, fibre-optical probe 11, probe tube
12nd, near infrared spectrometer 13, effect circulation house steward 14, two effect circulation house steward 14 ' and steam pipework；Concentrator one imitates heating chamber
5 pass through an effect circulation house steward 14 connects concentrator one effect vaporization chamber 6, and concentrator two effect heating chamber 5 ' always passes through two effect circulations
Pipe 14 ' connects concentrator two effect vaporization chamber 6 ', and concentrator one effect vaporization chamber 6 connects concentrator one by steam pipework 15
Effect heating chamber 5 ', circulation house steward's bypass 7 is connected to concentrator one effect heating chamber 5 and concentrator one effect with circulation branch road form
On an effect circulation house steward 14 between vaporization chamber 6, the first valve 1, the second valve 2, miniature magnetic driving gear pump 8, filter
9th, flow cell 10 is connected in circulation house steward's bypass 7 in a series arrangement, and flow cell 10 connects near infrared light by fibre-optical probe 11
Spectrometer 13, the 3rd valve 3, the 4th valve 4 and probe tube 12 are connected and are connected in circulation house steward's bypass 7 with branch road form, lean on
Nearly flow cell 10.
2. the online acquisition of near infrared spectrum and concentrated solution sample
After concentration starts, open the first valve 1 and the second valve 2, communication loop pipeline 7, concentrated solution passes through miniature magnetic
Driving gear pump 8 enters filter 9, reaches flow cell 10, near infrared spectrometer 13 online acquisition flow cell after filtering impurity
The near infrared spectrum of concentrated solution, during sampling, opens the 3rd valve 3, and solution to be concentrated closes the 3rd valve 3 after being full of probe tube 12,
Open the 4th valve 4, collect concentrated solution sample and be used for measuring every quality control index.Water precipitating liquor stream in flow cell 10 and circulation line
Speed controls in 120 ml/min, and filter is used for filtering the most of solid impurity granule in water precipitating liquid, and filtering accuracy is micro- for 60
Rice.
Near infrared spectrum is gathered using transmission beam method, spectral region is 4500 cm-1~12000 cm-1, scanning times are 32
Secondary, resolution is 8 cm-1, with air as reference.Spectrum and concentrated solution sample online acquisition divide three phases: the first stage, will
The extracting solution that Radix Salviae Miltiorrhizae, flos carthami water extraction obtain successively is introduced in an effect vaporization chamber 6 and two effect vaporization chambers 6 ' by vacuum, until
Tapping terminates, during every 5 minutes online acquisition near infrared spectrums, every 20 minutes from sample tap sampling；Second stage, will
Two effect vaporization chambers 6 ' in concentrated solution suction one effect vaporization chamber 6 in, during every 2.5 minutes online acquisition near infrared spectrums,
Every 5 minutes from sample tap sampling；Phase III, after concentrated solution is fully transferred to an effect vaporization chamber 6, every 30 seconds online acquisition
Near infrared spectrum, samples from sample tap at intervals of two minutes, until medicinal liquid density reaches 1.27 ~ 1.28g/ml, concentration process terminates.
Collect the concentrated solution sample in different batches economic benefits and social benefits concentration process, randomly choose wherein 2 batch datas as checking collection,
Remaining sample participates in modeling as calibration set.Repeat the concentration experiment of 10 batches of DANHONG ZHUSHEYE, the experiment of every batch is all with identical
Mode is sampled and gathers spectrum.176 concentrated solution samples are obtained.
3. each quality control index measures
Each quality control index includes danshensu, protocatechualdehyde, Hydroxy Carthamus yellow a, rosmarinic acid, salvianolic acid b and aqueous
Rate.Danshensu, protocatechualdehyde, Hydroxy Carthamus yellow a, fan in concentrated solution sample is measured using high performance liquid chromatography (hplc)
Repeatedly fragrant acid and salvianolic acid b；Measure moisture content using weighting method after dried.
(1) high performance liquid chromatography: condition: agilent eclipse c18 analytical column (2504.6 mm, 5 μm)；
Flow velocity 1 ml/min；35 DEG C of column temperature；Sample size 5 μ l；Mobile phase: a is methanol, and b is 0.5% aqueous formic acid (v/v), 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%.Detection wavelength: 0 ~ 13 min, 280 nm(reference wavelength 360 nm)；13 ~ 21 min, 403 nm(reference wavelengths
500 nm)；21 ~ 45 min, 280 nm(reference wavelength 360 nm).
Concentrated solution sample is centrifuged 10 minutes in 1500 r/min high speed centrifuges, then is diluted to different multiples, filtration
(0.45 m microporous filter membrane), takes subsequent filtrate to be used for liquid phase analysis.
Specification Curve of Increasing: precision weighs danshensu, protocatechualdehyde, Hydroxy Carthamus yellow a, rosmarinic acid and pellet respectively
Phenolic acid b reference substance is appropriate, using mobile phase (methanol -0.5% formic acid, v/v, 50:50) dilution, makes the storage of single component reference substance
Standby liquid, storing solution proportional diluted is made into the working solution of variable concentrations, sample introduction analysis under above-mentioned chromatographic condition.With chromatographic peak
Area y carries out linear regression to sample introduction concentration x.Result shows, danshensu, protocatechualdehyde, Hydroxy Carthamus yellow a, Herba Rosmarini Officinalis
Acid and salvianolic acid b the range of linearity be respectively 9.84 ~ 147.6,1.13 ~ 22.68,3.74 ~ 37.41,4.83 ~ 57.98,52.80 ~
1056 μ g/ml, correlation coefficient r value is all higher than 0.9998.
(2) weighting method after dried: (after drying twice, weight differential is less than 5 mg, note to the weighing botle of weighed drying to constant weightx 0 ), measure 1 ml concentrated solution to flat bottle, weigh (x 1 ), dry to constant weight in 105 DEG C, take out and put cooling 30 in exsiccator
Min, weigh rapidly (x 2 ), moisture content according to the following formula:
4. set up relative density-moisture content canonical plotting
Choose the sample of different densities in 8 economic benefits and social benefits concentration processs, measure moisture content simultaneously, with density as vertical coordinate, contain
Water rate is abscissa Criterion curve, and the fit equation obtaining is:y=-0.005x+ 1.48,r 2 =0.9972.By above-mentioned
Equation understands, there is preferable dependency between relative density and moisture content.In actual production process, moisture content can be passed through
Draw rapidly the relative density of sample, result is shown in Fig. 2.
5. rejecting abnormalities spectrum
Acutely rocking due to equipment in economic benefits and social benefits concentration process, baseline drift in the spectrum being easily caused flow cell collection
Or burr obvious situations such as, thus causing 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 of measured value xi (1≤i≤n) meets vi ＞ wn σ, xi is considered
Abnormal data, 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 are 17 samples
This spectral singularity, 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
Using First derivative spectrograply, the filtering of norris derivative, deduct straight line and standard normal variable converter technique to spectrum
Pretreatment, for eliminating baseline drift, noise, solid particle size, surface scattering and change in optical path length etc. near infrared spectrum
Impact.After comparing the impact to quality control index for the different pretreatments method, finally determine danshensu, Hydroxy Carthamus yellow a,
The preprocessing procedures of rosmarinic acid and salvianolic acid b model include: first derivative, standard normal variable conversion and norris lead
Number Filtering Processing；The preprocessing procedures of protocatechualdehyde model include: first derivative and deduct straight line；Moisture content model
Preprocessing procedures include: first derivative.
Following wave band: 4500 ~ 5445 cm need to be excluded when selecting modeling wave band-1With 7500 ~ 12000 cm-1Wave band, that is,
Two " water peak ".By the combined crosswise test of wave band, determine danshensu, protocatechualdehyde, Hydroxy Carthamus yellow a, Herba Rosmarini Officinalis
The modeling wave band of acid, salvianolic acid b and moisture content model is 5446.2 ~ 6101.9 cm-1With 7498.2 ~ 9403.6 cm-1.
7. each quality control index overall situation quantitative calibration models are set up using partial least-squares regression method
Near infrared spectrum data after pretreatment, sets up danshensu, protocatechualdehyde, hydroxyl using least square regression red
The overall quantitative calibration models of anthoxanthin a, rosmarinic acid, salvianolic acid b and moisture content, model correction result is referring to table 1.From table
In as can be seen that the correlation coefficient of all index components is all higher than 0.98, and calibration set relative deviation is respectively less than 10%.Document table
Bright calibration model rpd value thinks that more than 3 institute established model is preferable, herein the rpd value of positive model for school building be all higher than 7, from certain
Illustrate the stability of model preferably it is adaptable to actual production process on-line checking in degree.
8. each quality control index variation tendency in on-line analyses economic benefits and social benefits concentration process
By Suo Jian world model be used for danshensu in 1 batch of DANHONG ZHUSHEYE economic benefits and social benefits concentration process of on-line analyses, protocatechualdehyde,
Hydroxy Carthamus yellow a, rosmarinic acid, salvianolic acid b concentration and moisture content, predict the outcome as shown in Fig. 3 ~ 8.Can from figure
Go out, the anticipation trend of each quality control index is basically identical with the variation tendency of measured value.Itself rmsep and rsep value is referring to table 2, rsep
All control within 10%, fully meet the required precision of Chinese Traditional Medicine analysis in real time, illustrate that Suo Jian world model has
Higher prediction accuracy.
Embodiment 2:
According to the method for embodiment 1, it is in place of difference, using principal component analytical method, concentrated solution sample is divided into height
Concentration two class, sets up the partial model of each quality control index respectively according to classification.
1. spectrum principal component analysiss
Principal component analysiss are carried out to the 176 concentrated solution samples collecting, referring to figure, the first principal component of high density sample
Score value is higher, and the first principal component value of low-density sample is relatively low, and with first principal component score value 0.3 as boundary, high-concentration and low-concentration is (close
Degree) sample is divided into two classes.The above results show, the sample larger to concentration span, and segmentation modeling may obtain than global modeling
Obtain more excellent predictive ability.
2. each quality control index Local Quantitative calibration model is set up using partial least-squares regression method
As can be seen that because sample concentration scope is excessive, built quantitative model predicts effect in low concentration region from Fig. 3 ~ 8
Fruit higher concentration region is poor.Therefore, for principal component analysiss result, to low concentration group concentrated solution sample and high concentration group concentrated solution
Sample separately models again.The Local Quantitative model performance parameter evaluation of each quality control index is referring to table 3.Due to the too high appearance of factor number
It is easily caused model over-fitting, reduce the overall estimated performance of model on the contrary.From table 3 it is observed that it is only to choose low concentration region
Stand after setting up quantitative calibration models, the factor number of target component is all largely reduced.The performance of model so will be made
Further lifted.
3. partial correction model is predicted to unknown sample
Built partial model is used for analyzing the concentration change with 6 special quality control indexs in 1 batch of economic benefits and social benefits concentration process sample, its
Middle and high concentration sample pattern is used for predicting the high concentration sample in economic benefits and social benefits concentration process, low concentration model is used for predicting low concentration sample
This, predict the outcome referring to Figure 10 ~ 15, itself rmsep and rsep is referring to table 4.In addition to protocatechualdehyde with moisture content, remaining 4 special quality control
The prediction effect of index is all largely improved.The undesirable possible cause of the prediction effect of protocatechualdehyde be due to it
Concentration in system is too low, is easily disturbed by the content information of other compositions, thus affecting the prediction accuracy of model.This is real
The result tested shows, if the concentration range of sample is larger, takes local segmentation to model so that the predictive ability of model obtains relatively
Significantly lifted.Meanwhile, can deduce from the modeling result of protocatechualdehyde, due near infrared spectrum itself limitation (detection
Limit > 0.1%), the low concentration composition in complex matrices has the not enough danger of prediction.
.
Claims (3)
1. a kind of DANHONG ZHUSHEYE economic benefits and social benefits concentration process online test method is it is characterised in that realized by following steps:
(1) design near infrared online detection device
This device include the first valve (1), the second valve (2), the 3rd valve (3), the 4th valve (4), one effect heating chamber (5),
One effect vaporization chamber (6), two effects heating chamber (5 '), two effects vaporization chamber (6 '), circulation house steward's bypass (7), miniature magnetic driving gear
Pump (8), filter (9), flow cell (10), fibre-optical probe (11), probe tube (12), near infrared spectrometer (13), an effect circulation
House steward (14), two effects circulation house steward (14 ') and steam pipework, effect heating chamber (5) is passed through effect circulation house steward (14) and is connected one
Effect vaporization chamber (6), two effects heating chamber (5 ') are passed through two effects circulation house steward (14 ') and are connected two effects vaporization chamber (6 '), an effect vaporization chamber
(6) effect heating chamber (5 ') is connected by steam pipework (15), circulation house steward's bypass (7) is connected to an effect with circulation branch road form
In effect circulation house steward (14) between heating chamber (5) and effect vaporization chamber (6), the first valve (1), the second valve (2), miniature
Gear pump driven by magnetic force (8), filter (9), flow cell (10) are connected in circulation house steward's bypass (7) in a series arrangement, circulation
Pond (10) connects near infrared spectrometer (13), the 3rd valve (3), the 4th valve (4) and probe tube by fibre-optical probe (11)
(12) connect and be connected in circulation house steward's bypass (7) with branch road form, near flow cell (10)；
(2) online acquisition NIR transmittance spectroscopy and concentrated solution sample
After concentration starts, open the first valve (1) and the second valve (2), communication loop house steward bypasses (7), concentrated solution passes through micro-
Type gear pump driven by magnetic force (8) enters filter (9), reaches flow cell (10), near infrared spectrometer (13) exists after filtering impurity
Line gathers the near infrared spectrum of concentrated solution in flow cell, during sampling, opens the 3rd valve (3), and solution to be concentrated is full of probe tube
(12) close the 3rd valve (3) afterwards, open the 4th valve (4), collect concentrated solution sample and be used for measuring every quality control index, circulation
In pond (10) and circulation line, water precipitating flow velocity controls in 120 ml/min, and filtering accuracy is 60 microns；
Wherein near infrared spectral range is 4500 cm-1~12000 cm-1, scanning times are 32 times, and resolution is 8 cm-1, with sky
Gas is reference；
(3) detection concentrated solution sample in each quality control index: quality control index be danshensu, protocatechualdehyde, Hydroxy Carthamus yellow a,
Rosmarinic acid, salvianolic acid b and moisture content,
A () adopts high effective liquid chromatography for measuring danshensu, protocatechualdehyde, Hydroxy Carthamus yellow a, rosmarinic acid and salvianolic acid
b；Concentrated solution sample is centrifuged 10 minutes in 1500 r/min high speed centrifuges, then is diluted to different multiples, 0.45 m micropore filter
Membrane filtration, takes subsequent filtrate to be used for liquid phase analysis, by drawing standard curve, records each quality control index concentration；
Chromatographic condition: agilent eclipse c18 analytical column, 2504.6 mm, 5 μm；Flow velocity 1 ml/min；Column temperature 35
℃；Sample size 5 μ l；Mobile phase: a is methanol, and b is 0.5% aqueous formic acid of 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%；Detection wavelength:
0 ~ 13 min, 280 nm；13 ~ 21 min, 403 nm；21 ~ 45 min, 280 nm；
B () weighting method after dried measures moisture content: the weighing botle of weighed drying to constant weight, after drying twice, weight differential is less than 5
Mg, notex 0 , measure 1 ml concentrated solution to flat bottle, weighx 1 , dry to constant weight in 105 DEG C, take out and put cooling in exsiccator
30 min, weigh rapidlyx 2 , moisture content according to the following formula:
Moisture content (%)=(x 1 -x 2 )/(x 1 -x 0 ) ×100%；
(4) rejecting abnormalities spectrum:
Calculate the mahalanobis distance of original near infrared spectrum, and use Schottky photodetectors rejecting abnormalities spectrum, if measured value xi's is residual
Difference meets vi ＞ wn σ, and then xi is considered abnormal data, is rejected, and wherein, vi is residual error, and σ is standard deviation, and wn can table look-up
Arrive；1≤i≤n in wherein xi；
(5) selection near infrared spectrum modeling wave band and preprocess method:
Using First derivative spectrograply, norris derivative filtering, deduct straight line and standard normal variable converter technique to spectrum pre- place
Reason, for eliminating the impact near infrared spectrum such as baseline drift, noise, solid particle size, surface scattering and change in optical path length,
Danshensu, the preprocessing procedures of Hydroxy Carthamus yellow a, rosmarinic acid and salvianolic acid b model are: first derivative, standard
Normal variate conversion and norris derivative Filtering Processing；The preprocessing procedures of protocatechualdehyde model are: first derivative and subtracting
Remove straight line；The preprocessing procedures of moisture content model are: first derivative；
Danshensu, protocatechualdehyde, Hydroxy Carthamus yellow a, the modeling wave band of rosmarinic acid, salvianolic acid b and moisture content model are
5446.2~6101.9 cm-1With 7498.2 ~ 9403.6 cm-1；
(6) set up each quality control index model using Multivariate Correction algorithm, and using each model-evaluation index investigation model performance:
Each quality control index model is set up using partial least-squares regression method, model-evaluation index includes: model-evaluation index includes
Correlation coefficient r, calibration set root-mean-square error rmsec, calibration set are mutually authenticated root-mean-square error rmsecv, calibration set relative deviation
Rsec, relation analysis error rpd, when r value is less than rmsecv value close to 1, rmsec value, and both are as little as possible, and rsec is less than
When 20%, rpd >=3, stability and precision of prediction that institute's established model had are described, can be used for DANHONG ZHUSHEYE concentration process
On-line checking；
(7) established model is used for the variation tendency of each quality control index in on-line analyses DANHONG ZHUSHEYE economic benefits and social benefits concentration process:
The atlas of near infrared spectra of online acquisition DANHONG ZHUSHEYE concentrated solution, spectroscopic data is input in calibration model, Jing Guoji
Calculate the information learning each quality control index in concentrated solution in real time；
Online acquisition NIR transmittance spectroscopy wherein described in step (2) and concentrated solution sample divide three phases: the first stage, will
The extracting solution that Radix Salviae Miltiorrhizae, flos carthami water extraction obtain successively is introduced in effect vaporization chamber (6) and two effects vaporization chamber (6 ') by vacuum,
Until tapping terminates, during every 5 minutes online acquisition near infrared spectrums, every 20 minutes from sample tap sampling；Second-order
Section, by the concentrated solution suction one effect vaporization chamber (6) in two effects vaporization chamber (6 '), during near every 2.5 minutes online acquisition
Infrared spectrum, every 5 minutes from sample tap sampling；Phase III, after concentrated solution is fully transferred to an effect vaporization chamber (6), every
30 seconds online acquisition near infrared spectrums, sample from sample tap at intervals of two minutes, until medicinal liquid density reaches 1.27 ~ 1.28g/ml, dense
Compression process terminates.
2. a kind of DANHONG ZHUSHEYE economic benefits and social benefits concentration process online test method according to claim 1 is it is characterised in that walk
Suddenly (a) standard curve is drawn: weighs danshensu, protocatechualdehyde, Hydroxy Carthamus yellow a, rosmarinic acid and salvianolic acid b respectively
Reference substance, using methanol -0.5% formic acid, the flowing phase dilution of v/v, 50:50, makes single component reference substance storing solution, will store up
Standby liquid proportional diluted, is made into the working solution of variable concentrations, sample introduction analysis under above-mentioned chromatographic condition, with chromatographic peak area y to entering
Sample concentration x carries out linear regression, records danshensu, protocatechualdehyde, the line of Hydroxy Carthamus yellow a, rosmarinic acid and salvianolic acid b
Property scope be respectively 9.84 ~ 147.6,1.13 ~ 22.68,3.74 ~ 37.41,4.83 ~ 57.98,52.80 ~ 1056 μ g/ml, related
Coefficient r value is all higher than 0.9998.
3. a kind of DANHONG ZHUSHEYE economic benefits and social benefits concentration process online test method according to claim 1 it is characterised in that: step
Suddenly (6) set up each quality control index model using partial least-squares regression method, and concentration classification is not pressed for concentrated solution sample by world model,
It is completely used for modeling, partial model is, using principal component analytical method, according to concentration level, concentrated solution sample is divided into two classes, presses
Set up the partial model of each quality control index according to classification respectively, when world model's performance is not good, can be improved using partial model
Model performance and predictive ability.
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