Using Raman Spectroscopy To Detect Liquid Preparations
author: Joy
2022-01-06
Raman spectroscopy is a scattering technique. When a laser beam hits a sample, it scatters. Most of the energy of the scattered light does not change, and only a small part of the energy of the scattered light (less than 106 of the total) changes, which corresponds to the characteristic vibration of the molecule The sampling point of The Raman test is located at the focal point of the laser beam. With different optical designs, the focus length can vary within a range of a few millimeters or more. Therefore, the Raman spectrum can be used to realize the nondestructive measurement of the object by selecting the appropriate focal length of the fiber optic probe. Therefore, Raman spectroscopy is the best and probably the only choice for nondestructive identification of liquid preparations by packaging. If we can makegood use of Raman spectroscopy to establish a qualitative and quantitative modelfor nondestructive identification of liquid preparations by packaging, it will have a very broad application prospect.
Principle:
1. A method for the detection of liquid preparations by Raman spectroscopy comprises the following steps:
1) Obtain the Raman spectra required by this method.
1. A method for the detection of liquid preparations by Raman spectroscopy comprises the following steps:
1) Obtain the Raman spectra required by this method.
2) Qualitative identification: Compare the Raman spectra of the active ingredients in liquid preparations with the reference Raman spectra,and calculate the two.According to the correlation coefficient, the active ingredients in liquid preparations were qualitatively identified.
3) Quantitative calculation of the concentration of each component in the liquid preparation.
2. Liquid preparations include: injection, oral liquid preparations, external liquid preparations, etc
3. Packaging of liquid preparations includes: packaging bottles or bags, etc.
4. Using Raman spectroscopy technology, establish qualitative and quantitative model, through packaging nondestructive identification of liquid preparations in the inspection.
5. In the process of measurement, the API standard was dissolved in water solution for testing, and then the signal of subtraction water was obtained Raman reference spectrum, and stable and reliable spectrum and data were obtained.Choose water in liquid preparation as internal standard, which can well solve the problem that the Raman signal of the same sample will change correspondingly when the laser intensity changes, different probe or test light path changes.
Specific Practice：
1. Spectrum Required to Build the Model
A Raman spectrum of the liquid product, nondestructively measured through the bottle, includes Raman signals from the active ingredient (API), excipients, water and the bottle. In order to identify the API or excipient, the Raman signals from the API and excipient are separated from the overall Raman spectrum.
(1) The spectra of pure water and glass bottles need to be obtained first: A. Pour the pure water into the colorimetric dish for Raman detection, and measure the Raman spectrum of the pure water (represented by W); B. The empty bottle is directly Raman detection, get the Raman spectrum of the empty ampoule or glass bottle (toB).
2. Liquid preparations include: injection, oral liquid preparations, external liquid preparations, etc
3. Packaging of liquid preparations includes: packaging bottles or bags, etc.
4. Using Raman spectroscopy technology, establish qualitative and quantitative model, through packaging nondestructive identification of liquid preparations in the inspection.
5. In the process of measurement, the API standard was dissolved in water solution for testing, and then the signal of subtraction water was obtained Raman reference spectrum, and stable and reliable spectrum and data were obtained.Choose water in liquid preparation as internal standard, which can well solve the problem that the Raman signal of the same sample will change correspondingly when the laser intensity changes, different probe or test light path changes.
Specific Practice：
1. Spectrum Required to Build the Model
A Raman spectrum of the liquid product, nondestructively measured through the bottle, includes Raman signals from the active ingredient (API), excipients, water and the bottle. In order to identify the API or excipient, the Raman signals from the API and excipient are separated from the overall Raman spectrum.
(1) The spectra of pure water and glass bottles need to be obtained first: A. Pour the pure water into the colorimetric dish for Raman detection, and measure the Raman spectrum of the pure water (represented by W); B. The empty bottle is directly Raman detection, get the Raman spectrum of the empty ampoule or glass bottle (toB).
(2) In addition, a whole Raman spectrum including API, water and bottle is required:
A nondestructive Raman spectrum is obtained by Raman testing in a bottle (containing a liquid preparation)DWB stands for).
A nondestructive Raman spectrum is obtained by Raman testing in a bottle (containing a liquid preparation)DWB stands for).
(3) Finally, API or API standard material (API reference Raman spectroscopy) spectrum and the corresponding auxiliary Material reference Raman spectrum:
A. API's Raman spectrum (denoted by D) can be obtained by spectral subtraction; B. The API standard is configured into an aqueous solution with the same concentration, and then placed in a colorimetric dish for Raman test, to obtain the spectrum of Raman signal containing THE API standard and water, represented by RDW; The reference Raman spectra of the excipient standard aqueous solution were obtained in the same way, represented by REW. C. API reference Raman spectra (RD) and excipient reference Raman spectra (RE) can be obtained by means of spectral subtractions The standard substance is in solid state, and the Raman spectrum measured in solid state cannot be directly used in the method of the invention, because the Raman spectrum of the substance dissolved in an aqueous solution is different from the Raman spectrum of the substance in solid state, especially for the material in crystalline state, so it is necessary to put the API Two methods can be used to obtain the Raman spectrum of THE API standard. One is when the API standard is easy to obtain, dissolve it in an aqueous solution for testing, and then subtract the water signal; Second, if the API standard is difficult to obtain or expensive, you can take out the liquid preparation samples certified by other methods and pour them into a colorimetric dish for testing, and then reduce the signal of the water and the signal of the auxiliary materials.
2. Acquisition ofAPI Raman spectrum and API standard reference Raman spectrum Spectral subtraction fitting was performed according to the following formula:
D = a * DWB - b* W-c*W Formula (1)
RD = d * RDW - f * W Formula (2)
Where a, b, C, D and f are subtraction fitting coefficients. Thus, the Raman spectra of API in liquid preparation samples and the reference Raman spectra of API standard substances were obtained respectively.
3. Qualitative identification
Test Result:
A. API's Raman spectrum (denoted by D) can be obtained by spectral subtraction; B. The API standard is configured into an aqueous solution with the same concentration, and then placed in a colorimetric dish for Raman test, to obtain the spectrum of Raman signal containing THE API standard and water, represented by RDW; The reference Raman spectra of the excipient standard aqueous solution were obtained in the same way, represented by REW. C. API reference Raman spectra (RD) and excipient reference Raman spectra (RE) can be obtained by means of spectral subtractions The standard substance is in solid state, and the Raman spectrum measured in solid state cannot be directly used in the method of the invention, because the Raman spectrum of the substance dissolved in an aqueous solution is different from the Raman spectrum of the substance in solid state, especially for the material in crystalline state, so it is necessary to put the API Two methods can be used to obtain the Raman spectrum of THE API standard. One is when the API standard is easy to obtain, dissolve it in an aqueous solution for testing, and then subtract the water signal; Second, if the API standard is difficult to obtain or expensive, you can take out the liquid preparation samples certified by other methods and pour them into a colorimetric dish for testing, and then reduce the signal of the water and the signal of the auxiliary materials.
2. Acquisition ofAPI Raman spectrum and API standard reference Raman spectrum Spectral subtraction fitting was performed according to the following formula:
D = a * DWB - b* W-c*W Formula (1)
RD = d * RDW - f * W Formula (2)
Where a, b, C, D and f are subtraction fitting coefficients. Thus, the Raman spectra of API in liquid preparation samples and the reference Raman spectra of API standard substances were obtained respectively.
3. Qualitative identification
Test Result:
Fig 1Raman Spectra ofDoxofylline Injection Measured in Ampoule (DWB)Empty Ampoule
Bottle.Raman Spectrum (B); Raman Spectroscopy ofPure Water (W);Spectrum ofPure Doxofylline
(API) (D)
Fig 2Raman Spectroscopy (RDW) ofDoxofylline API in Aqueous Solution in A Colorimetric Dish;
pure.Raman Spectroscopy ofWater (W); Standard Spectrum (RD) ofDOxofylline (API) Obtained by
Subtraction
Fig 3Raman spectrum (DWB) of zinc gluconate oral solution measured through glass bottle; Raman
spectra of empty glass bottles (B); Raman spectroscopy ofpure water (W); Raman spectra ofpure zinc
gluconate (API) (D); Raman Spectroscopy (RE) of Pure Sucrose (Excipient)
Fig 4Raman Spectra ofZinc Gluconate (API) Standard Aqueous Solution in A Colorimetric
Dish(RDW); Raman Spectroscopy ofPure Water (W); Standard Spectrum (RD) ofZinc Gluconate
(API) Obtained by Reduction
Fig 5Raman Spectroscopy (RDW) of Sucrose (Excipient) Standard a Aqueous Solution In A
Colorimetric Dish; Pure Water.The Raman Spectrum (W) was Subtracted from Tthe Standard Spectrum
(RD) of Sucrose (Excipients).
Fig 6Raman Spectrum (DWB) ofDoxofylline Glucose LVP Measured by Packaging, Null
Raman Spectrum ofWhite Packaging Bag (B), Raman Spectrum ofPure Water (W), Raman Spectrum
ofPure Glucose (Excipient) (RE), Pure Polysol
Raman Spectrum (RD) ofTheophylline (API).
Conclusion:
In order to quickly screen fake and inferior injection, it is hoped that the active pharmaceutical ingredients and excipients of liquid preparation in packaging bottle can be directly identifiedwithout damaging the package totake out the sample.Since the NIR spectrum is an absorption spectrum, it is usually measured in transmission or reflection mode for the clarified liquid. The measured optical path depends on the diameter of the bottle for injection. Usually, the bottle for liquid preparation is large (from 1mL to 500mL), so the measured optical path is too large to obtain the required NIR spectrum. Therefore,for liquid preparations, especially for larger packages, NIR technology cannot be a universal solution. Midinfrared spectroscopy can effectively analyze liquid samples using ATR attachments.The midinfrared spectrum has high absorption efficiency, so the optical path measured during testing is usually only a few microns, and the wall thickness of the bottle varies from a few tenths of a millimeter to a few millimeters. Therefore, the midinfrared ATR technology cannot penetrate the bottle wall to achieve nondestructive testing, and the sample needs to be removed from thepackage.Raman spectrometers can be used directly on the bottled liquid preparations of the active drug.Ingredients (API) and excipients are nondestructively identified without breaking the package to remove the sample.
Microscopic Raman Spectroscopy for Graphene Sample Testing - Get the principles and applications of ATR
- Optimising confocal Raman microscopy for spectral mapping of cement-based materials
- Application of Confocal Micro Raman Spectroscopy in Interface Research
- Existing Standards,Guides and Practices for Raman Spectroscopy
- ATR8800 Raman Imaging Technology
- Raman Spectroscopy and its Most Common Applications
Raman : Applications 
Application of Raman Spectroscopy in Characterization of Graphene Structure 
Food Analysis and Raman Spectroscopy 
Raman or FTIR Spectroscopy 
What is Raman Spectroscopy? 
Raman spectroscopic detection and analysis of Scutellaria baicalensis herbal tablets 
What is X-ray Fluorescence (XRF) 
What is the Raman microscope? 
What is the SERS？ 
(Suzhou Institute of Biomedical Engineering Technology, Chinese Academy of Sciences)Escherichia coli sample and Staphylococcus aureus Raman spectrum detection report on silver substrate 
What Is Raman Spectroscopy Used For? 
Test Report of Insulating Oil and Insulating Paper of Electrical Engineering College of Chongqing University 
ATR8300-1064 high sensitive near-infrared microRaman spectrometer was used to rapidly identify textile components