CN112782130A

CN112782130A - Method for detecting moisture content of intermediate powder of tendon-relaxing and waist-strengthening pill by adopting NIR (near infrared ray)

Info

Publication number: CN112782130A
Application number: CN202011621233.5A
Authority: CN
Inventors: 林建云; 江森; 雷胄熙; 陈蓉蓉
Original assignee: Guangzhou Baiyunshan Chen Liji Pharmaceutical Factory Co ltd
Current assignee: Guangzhou Baiyunshan Chen Liji Pharmaceutical Factory Co ltd
Priority date: 2020-12-30
Filing date: 2020-12-30
Publication date: 2021-05-11

Abstract

The invention provides a method for detecting the moisture content of intermediate powder of a muscle-relaxing and waist-strengthening pill by adopting NIR (near infrared spectroscopy), and relates to the field of pharmaceutical analysis. The method comprises the following steps: s1, scanning a plurality of batches of intermediate powder samples of the tendon-relaxing waist-strengthening pills to obtain near infrared spectrums; s2, respectively measuring the moisture content values of the samples by adopting a drying method; s3, establishing a correction model between the characteristic spectrum of the comfort infrared spectrum and the moisture content value thereof by adopting a partial least square method; s4, inputting the near infrared spectrum of the verification set into a correction model to obtain a predicted value of the moisture content of the sample of the verification set; comparing with the moisture value measured by the verification set sample drying method, judging whether the verification set sample is an out-of-bounds point, and adding the out-of-bounds point to reestablish the correction model according to the step S3 when the verification set sample is determined to be the out-of-bounds point; s5, scanning the near infrared spectrogram of the middle powder sample of the tendon-relaxing and waist-strengthening pill to be detected, inputting the spectrogram into the correction model, and obtaining the moisture content value. The method of the invention can rapidly detect and monitor the moisture on line, and has the advantages of simple and rapid operation, rapid analysis speed, high efficiency, strong stability and the like.

Description

Method for detecting moisture content of intermediate powder of tendon-relaxing and waist-strengthening pill by adopting NIR (near infrared ray)

Technical Field

The invention belongs to the field of drug analysis, and particularly relates to a method for detecting the moisture content of intermediate powder of a muscle-relaxing and waist-strengthening pill by adopting NIR (near infrared spectroscopy).

Background

The muscle-relaxing waist-strengthening pill is a unique product of Guangzhou Baiyunshan Chenli pharmaceutical factory, which consists of 13 medicines of rhizoma cibotii, cherokee rose fruit, caulis spatholobi, philippine flemingia root, beautiful millettia root, glossy privet fruit (steamed), Chinese taxillus twig (steamed), south dodder seed (processed by salt), corydalis tuber (processed), radix zanthoxyli, frankincense (processed), myrrh (processed) and the like, has the functions of tonifying liver and kidney, strengthening muscles and bones, dispelling wind and removing dampness, activating collaterals and relieving pain, and can be used for relieving soreness and pain of waist and knees. The moisture content of the muscle-relaxing and waist-strengthening pill is detected by a drying method of a water content determination method of the four parts 0832 of China pharmacopoeia of 2020 edition, the drying method needs more than 7 hours, the defects of energy consumption, time consumption, complex operation, sample damage and the like exist, and the moisture content value of the muscle-relaxing and waist-strengthening pill cannot be quickly reflected. The defects are not favorable for carrying out online or rapid quality analysis in the production process of the muscle-relaxing and waist-strengthening pill, improve the production efficiency and are not suitable for the requirement of modern production and development of traditional Chinese medicines. Therefore, a new method for analyzing and detecting the moisture content of the muscle-relaxing and waist-strengthening pill, which is rapid, efficient and accurate, is urgently needed to be researched.

Near Infrared spectroscopy (NIR) analysis technology is a test technology rapidly developed in the later 80 th of the 20 th century, and the Near Infrared spectroscopy (12000-4000 cm) of a measured substance is measured^-1) The characteristic spectrum of the substance is extracted by using a proper chemometric method, and then the substance to be detected is qualitatively and quantitatively analyzed. Common measurement techniques for near infrared spectroscopy include transmission, diffuse reflection, and reflectance-transmission. The transmission method is suitable for analyzing transparent liquid samples; diffuse reflectance methods are used primarily for analysis of solid and semi-solid samples. The method comprises the steps of irradiating a sample to be detected by adopting near infrared light, obtaining an absorption spectrum in a near infrared region in a diffuse emission mode by utilizing the universal frequency vibration or rotation of chemical bonds such as O-H, N-H contained in an organic matter, and establishing a linear or nonlinear model between a substance spectrum and the content of a component to be detected by using multiple linear regression and other metering means, thereby realizing the rapid calculation of the content of the component to be detected by using the near infrared spectrum information of the substance.

The near infrared spectrum technology is a rapid and nondestructive analysis technology, sample analysis can be completed within 1 minute, a plurality of parameters are measured, the detection time is shortened, the production efficiency is improved, the input cost of manpower and material resources is reduced, the pretreatment of samples is not required to be carried out by using reagents or solvents, the emission of harmful wastes is reduced, and the method is green and environment-friendly. Not only can off-line analysis be carried out, but also on-line process control can be directly carried out. The method not only can directly measure active ingredients in raw materials and preparations, but also can analyze certain physicochemical properties of the medicine, such as moisture, hydroxyl value and acid value of fatty compounds, and the like, and can provide chemical and physical information of samples.

Disclosure of Invention

Therefore, in order to solve the above problems, a method for detecting the moisture content of the intermediate powder of the muscle-relaxing and waist-strengthening pill by using NIR is provided, which can realize rapid detection of the moisture content of the intermediate powder of the muscle-relaxing and waist-strengthening pill, realize continuous production, and improve the production efficiency.

The invention provides a method for detecting the moisture content of intermediate powder of a muscle-relaxing and waist-strengthening pill by adopting NIR (near infrared spectroscopy), which comprises the following steps of:

s1, scanning a plurality of batches of intermediate powder samples of the muscle-relaxing waist-strengthening pills by using a near-infrared spectrometer to obtain a corresponding near-infrared spectrum;

s2, respectively measuring the moisture content value of the middle powder sample of each batch of the tendon-relaxing and waist-strengthening pills by adopting a drying method;

s3, establishing a correction model between the near infrared spectrum characteristic spectrum of the tendon-relaxing and waist-strengthening pill intermediate powder sample and the moisture content value thereof by adopting a partial least square method;

s4, inputting the near infrared spectrum of the intermediate powder of the tendon-relaxing and waist-strengthening pills in the verification set into a correction model to obtain a predicted value of the moisture content of a sample in the verification set; comparing with the moisture value measured by the verification set sample drying method, judging whether the verification set sample is an out-of-bounds point, adding the out-of-bounds point when the verification set sample is determined to be the out-of-bounds point, reestablishing the correction model according to the step S3, and perfecting the correction model;

s5, scanning the middle powder sample of the tendon-relaxing and waist-strengthening pill to be detected by using a near-infrared spectrometer to obtain a corresponding near-infrared spectrogram, and inputting the corresponding near-infrared spectrogram into the S4 correction model to obtain the moisture content value of the middle powder sample of the tendon-relaxing and waist-strengthening pill to be detected.

Wherein, the intermediate powder of the muscle-relaxing waist-strengthening pill is as follows: is prepared from 13 Chinese medicinal materials including rhizoma Cibotii, fructus Rosae Laevigatae, caulis Spatholobi, radix Flemingiae Philippinensis, caulis Kadsurae Coccineae, radix Millettiae Speciosae, fructus Ligustri Lucidi (steamed), herba Taxilli (steamed), semen Cuscutae (processed with salt), rhizoma corydalis (processed), radix Zanthoxyli, Olibanum (processed), and Myrrha (processed).

In one embodiment, the near infrared spectrum is measured by a fourier transform near infrared spectrometer in step S1.

In one embodiment, in step S1, the particle size of the tendon-relaxing and waist-strengthening pill intermediate powder is 95.0% or more and passes through a 100-mesh sieve, and 100.0% passes through an 80-mesh sieve.

In one embodiment, in the step S1, the number of batches of samples is greater than or equal to 30. Preferably, the number of batches of samples is ≧ 110.

In one embodiment, in step S1, the near infrared spectrum is measured by integrating sphere diffuse reflection with a resolution of 8cm^-1The scanning frequency is 64 times, and the scanning range is 12000-4000 cm^-1And repeatedly scanning for 2-3 times at 18-25 ℃, and taking an average spectrum.

In one embodiment, the drying method adopts a drying method in the 0832 moisture determination method in the fourth part of the 2020 edition "Chinese pharmacopoeia".

In one embodiment, in step S2, the drying method specifically includes: spreading 2-5 g of tendon-relaxing waist-strengthening pill intermediate powder in a dry weighing bottle, drying at 100-110 ℃ for 4-6 h, cooling after drying, weighing, and calculating a weighing difference; when the weighing difference of two continuous times is less than or equal to 5mg, calculating the water content value in the sample; and when the weight difference of two successive times is more than 5mg, continuously drying for 1-2 h at 100-110 ℃, weighing, calculating the weight difference until the weight difference of two successive times is not more than 5mg, and calculating the water content value in the sample.

In one embodiment, in step S3, the main factor number of the correction model is determined according to the correlation diagram between the correction set RMSECV and the main factor number, the main factor of the correction model is 6, and the internal cross-validation mean square error RMSECV is 0.152;

moisture determination coefficient R of the established correction model²≥0.9500。

Preferably, in step S3, the correction model has a main factor number of 6, RMSEP of 0.106, and R²The RMSECV was 0.9986, and was 0.152.

In one embodiment, in the step S3, the quantitative near infrared quantitative analysis model is established, and the predicted value of the validation set sample has a relative error of not more than 5% with the average value of moisture determined by the drying method.

In one embodiment, in step S4, the average relative error (%) between the predicted value of the preferred calibration model validation set sample and the moisture value determined by the drying method is 1.89%.

In one embodiment, the on-line detection is achieved by mounting the assay probe on the production line; and measuring the near infrared spectrogram of samples of different batches by random sampling; and inputting the near-infrared spectrogram into the correction model to obtain the water content value of the near-infrared spectrogram, so as to realize quick detection.

Compared with the prior art, the invention has the following beneficial effects:

the detection method does not need to pretreat the tendon-relaxing and waist-strengthening pill intermediate powder sample, is simple, convenient and quick to operate, high in analysis speed (sample analysis can be completed within 1 minute), high in efficiency, free of damage to the sample, low in cost, free of pollution and convenient to realize online analysis, and the relative error between the predicted value of the sample and the average value of the moisture measured by a drying method is verified to be not more than 5% by the established quantitative near infrared quantitative analysis model, so that online rapid detection and monitoring of the moisture can be realized, the moisture content of the sample is controlled, the product quality is ensured, the production process can be timely switched to the next production procedure, the production period is shortened, the time consumed by the original traditional moisture measurement method is at least 7 hours, the time is reduced to within 1 minute, whether the moisture content of the sample is qualified or not can be measured, the production efficiency of the product is, Microbial contamination and the like.

Drawings

FIG. 1 is a NIR spectrum of the intermediate powder of 110 batches of the tendon-relaxing and waist-strengthening pills in the example;

FIG. 2 is a diagram of the relationship between the preferred muscle-relaxing and waist-strengthening pill center powder model RMSECV and the number of main factors in the embodiment;

FIG. 3 is a diagram showing the predicted value and the actual value of the moisture content of the model of the preferred tendon-relaxing and waist-strengthening pill powder in the embodiment;

FIG. 4 is a graph of the deviation of moisture content of the preferred muscle-relaxing and waist-strengthening pill center powder model in the example, relative to the real value.

Detailed Description

To facilitate an understanding of the invention, a more complete description of the invention will be given below in terms of preferred embodiments. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

Example 1

1. Collecting samples: 110 batches of intermediate powder samples of the muscle-relaxing waist-strengthening pills with different batches of numbers are collected.

2. Data collection was performed on 110 batches of samples: the near infrared spectrum of the sample in the calibration set was measured by a near infrared spectrum measuring instrument (MPA type Fourier transform near infrared spectrometer, BRUKER, Germany, light source: halogen tungsten lamp, detector: PbS, attached diffuse reflection integrating sphere, sample rotator and quartz sample cup). And (3) a sample measuring mode: integrating sphere diffuse reflection, resolution: 8cm^-1The number of scanning times: 64 times, scanning range: 12000-4000 cm^-1Room temperature: 18-25 ℃. Collecting original NIR spectrum of intermediate powder of muscle-relaxing and waist-strengthening pill by using near-infrared spectrometer, and repeatedly scanning each sampleDrawing 2-3 times, and taking the average spectrum. And (3) performing spectrum pretreatment and spectrum region selection by using OPUS7.5 analysis software to obtain characteristic spectrum information of the water content in the intermediate powder of the muscle-relaxing and waist-strengthening pill.

3. Moisture content value determination for 110 batches of samples: taking 2-5 g of 110 batches of the intermediate powder of the muscle-relaxing waist-strengthening pills, flatly paving the intermediate powder in a flat weighing bottle which is dried to constant weight, precisely weighing, opening a bottle cap, drying for 5 hours at 105 ℃, covering the bottle cap, moving the bottle cap into a dryer, cooling for 30 minutes, precisely weighing, drying for 1 hour at the temperature, cooling, weighing until the difference of two successive weighing is not more than 5 mg. The water content (%) of the test article was calculated from the weight loss (see table 1110. moisture value measured by drying the intermediate powder of the tendon-relaxing and waist-strengthening pill batch).

TABLE 1.110 moisture value of the middle powder drying method of tendon-relaxing waist-strengthening pill batch

Numbering	Moisture value (%)	Numbering	Moisture value (%)	Numbering	Moisture value (%)
						1	9.46	38	6.15	75	12.37
2	9.31	39	6.32	76	12.97
						3	9.29	40	6.40	77	13.38
4	9.19	41	5.78	78	13.38
						5	9.29	42	3.55	79	13.19
6	9.04	43	5.96	80	13.34
						7	8.93	44	3.21	81	13.02
8	9.10	45	2.30	82	13.35
						9	6.52	46	3.43	83	13.57
10	6.73	47	3.85	84	1.52
						11	6.74	48	2.84	85	1.52
12	7.21	49	3.39	86	2.24
						13	6.93	50	2.77	87	1.73
14	6.81	51	2.03	88	1.36
						15	2.68	52	1.19	89	1.84
16	2.24	53	1.61	90	1.75
						17	5.84	54	1.86	91	1.44
18	5.79	55	1.76	92	2.25
						19	2.91	56	2.28	93	2.19
20	2.71	57	2.41	94	1.74
						21	2.19	58	2.20	95	1.59
22	3.04	59	2.50	96	2.26
						23	3.11	60	2.77	97	1.89
24	2.45	61	1.84	98	2.20
						25	5.82	62	1.99	99	1.80
26	3.08	63	2.13	100	2.35
						27	6.11	64	1.85	101	1.66
28	3.78	65	2.24	102	1.72
						29	3.88	66	2.03	103	1.52
30	6.15	67	2.70	104	1.94
						31	6.32	68	1.82	105	1.77
32	6.40	69	1.85	106	1.95
						33	5.78	70	2.29	107	1.60
34	3.55	71	2.39	108	2.11
						35	5.96	72	2.13	109	1.75
36	6.11	73	13.29	110	2.29
						37	3.78	74	12.79

4. Establishing a correction model: the near infrared spectra of 110 batches of samples, except that 10 batches of samples were randomly selected for testing the sample set, the remaining 100 batches were subjected to Partial Least Squares (PLS) in chemometrics to establish a sample calibration model by correlating the moisture content values measured by the drying method with the characteristic spectra (Table 2. influence of different pretreatment methods and spectral range on the model).

TABLE 2 Effect of different pretreatment methods and spectral region ranges on the model

5. Selection of moisture content and optimal model for a test sample set

(1) Selecting a test sample set: based on the selection of representative samples for the calibration sample set, 10 samples were taken except for the calibration sample set. And checking whether the correction model is reliable or not through the checking sample set, checking the practical performance of the model and determining the optimal model.

The moisture content of the test sample set can be predicted by inputting the spectral feature map of the test sample set into the 4 calibration models of Table 2. And obtaining the correlation coefficient external verification mean square error (RMSEP) and deviation (Bias) of the NIR predicted value and the measured value of the pharmacopoeia drying method.

As can be seen from Table 3, the mean square deviations for external validation (RMSEP) and the deviations (Bias) are the same for the correction models I, II, III, IV, but the correction model I RMSECV is minimal, R is²And finally, determining that the correction model I is the optimal model.

TABLE 3 correlation coefficient of four correction models to the predicted results of the test sample set

Method	RMSEP	Bias	SEP	RPD
					Ⅰ	0.106	0.0247	0.105	20.6
Ⅱ	0.106	0.0247	0.105	20.6
					Ⅲ	0.106	0.0247	0.105	20.6
Ⅳ	0.106	0.0247	0.105	20.6

As can be seen from Table 4, the correction model I is used for predicting the moisture of 10 samples in the test sample set, the relative deviation between the measurement result of the pharmacopoeia drying method and the measurement result of the NIR spectroscopy is within plus or minus 5%, and the prediction result is accurate.

TABLE 4 prediction of the calibration model I on the test sample set

Scanning 110 batches of the collected middle powder samples of the tendon-relaxing waist-strengthening pills by using a near infrared spectrum detection instrument to obtain a corresponding NIR spectrogram, which is shown in figure 1. Selecting 10 batches of samples for testing out of the sample set according to the selection of representative samples of the correction sample set, applying OPUS7.5 analysis software to the remaining 100 batches of samples, correlating the NIR spectrum and the moisture content value of the correction sample set by using a PLS method to establish a quantitative correction model, and establishing a quantitative correction model according to the minimum RMSECV, R²Maximum, the more predicted resultAnd selecting an optimal model according to the principle of approaching the true moisture value. FIG. 2 is a graph showing the correlation between the optimal model RMSECV and the number of main factors, and it can be seen that when the number of main factors of the tendon-relaxing and waist-strengthening pill-based mean powder quantitative correction model is 6, the correction set RMSECV can be minimized. Correlation coefficient R of PLS quantitative correction model to moisture content of muscle-relaxing waist-strengthening pill intermediate powder²0.9986, the mean square error of internal cross validation (RMSECV) was 0.152, the number of major factors was 6, and there was a good correlation between the NIR spectrum of the middle powder of the Shujin Jianyao pill and its moisture content. Fig. 3 and 4 are a correlation diagram of an NIR predicted value and a moisture true value and a correlation diagram of an NIR deviation and a moisture true value obtained after interactive verification of a tendon-relaxing and waist-strengthening pill intermediate powder calibration set sample, respectively.

And (3) checking precision of the correction model: and (3) taking the same sample, repeatedly scanning the same sample by using a near infrared spectrometer for 6 times, inputting the obtained NIR spectrum into a water content correction model of the tendon-relaxing and waist-strengthening pill intermediate powder, and repeatedly calculating the NIR spectrum for 6 times, and inspecting the precision of the model, wherein the RSD value is 0.75% (n is 6). The results are shown in Table 5, and it is clear from Table 5 that the precision of the apparatus and the calibration model is good.

TABLE 5 precision test

And (3) checking repeatability of a correction model: and 6 parts of the same batch of samples are taken, scanning is respectively carried out by a near infrared spectrometer, the obtained NIR spectrum is input into a moisture content correction model of the tendon-relaxing and waist-strengthening pill intermediate powder to calculate the moisture content, and the RSD value is 1.33% (n is 6). The results are shown in Table 6, and it is understood from Table 6 that the reproducibility of the calibration model is good.

TABLE 6 reproducibility test

When the measuring environment of the sample is changed, the calibration model is checked by using the test sample set, if the prediction effect of the calibration model is reduced, the test sample is added to the calibration sample set, and the calibration model is modified according to the steps.

The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims

1. A method for detecting the moisture content of the intermediate powder of the muscle-relaxing and waist-strengthening pill by adopting NIR (near infrared spectroscopy), is characterized by comprising the following steps of:

2. The method according to claim 1, wherein in step S1, the near infrared spectrum is measured using a fourier transform near infrared spectrometer.

3. The method as claimed in claim 1, wherein in step S1, the particle size of the tendon-relaxing and waist-strengthening pill intermediate powder is 95.0% or more and passes through a 100-mesh sieve, and 100.0% and passes through an 80-mesh sieve.

4. The method according to claim 1, wherein the number of batches of the sample is greater than or equal to 30 in the step S1.

5. The method according to claim 1, wherein in step S1, the near infrared spectrum is measured by integrating sphere diffuse reflection with a resolution of 8cm^-1The scanning times are 32-64 times, and the scanning range is 12000-4000 cm^-1And repeatedly scanning for 2-3 times at 18-25 ℃, and taking an average spectrum.

6. The method as claimed in claim 1, wherein in step S2, the drying method is the drying method in the national pharmacopoeia of the fourth part 0832, 2020 edition.

7. The method according to claim 1, wherein in the step S2, the drying method specifically comprises: spreading 2-5 g of tendon-relaxing waist-strengthening pill intermediate powder in a dry constant-weight weighing bottle, drying at 100-110 ℃ for 4-6 h, cooling after drying, weighing, and calculating a weight difference; when the weighing difference of two continuous times is less than or equal to 5mg, calculating the water content value in the sample; and when the weight difference of two successive times is more than 5mg, continuously drying for 1-2 h at 100-110 ℃, weighing, calculating the weight difference until the weight difference of two successive times is not more than 5mg, and calculating the water content value in the sample.

8. The method according to claim 1, wherein in the step S3, the characteristic absorption spectrum range of the correction model is 8000-4000 cm^-1。

9. The method according to claim 1, wherein in step S3, the main factor number of the correction model is determined according to the correlation diagram between the correction set RMSECV and the main factor number, the main factor of the correction model is 6, and the internal cross-validation mean square error RMSECV is 0.152;

10. The method according to any one of claims 1 to 9, wherein the step S5 is further followed by a step S6: the near-infrared quantitative analysis model obtained in S3 is periodically verified and updated.