A method and system for rapid detection of triphenyl phosphate purity

Abstract

The present application relates to the technical field of rapid quantitative analysis of flame retardant purity, and discloses a rapid detection method and system for determining the purity of triphenyl phosphate, which comprises the following steps: automatically sampling from a triphenyl phosphate sample to be detected, grinding, dissolving, filtering and constant volume to obtain a pretreated sample, gradually diluting the pretreated sample to obtain a diluted sample, further separating the diluted sample by a high-performance liquid chromatograph at multiple wavelengths and identifying peaks in real time, calculating the purity value of the sample according to the identification result and self-verifying through cyclic detection, and finally automatically generating electronic records and encrypting and archiving them. Through the automatic closed-loop operation of the sampling-detection-reporting full module, the present application significantly improves the detection efficiency and accuracy, reduces solvent consumption and waste liquid discharge, and is suitable for the high-throughput, high-precision and traceable purity release requirements of the flame retardant industry.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of rapid quantitative analysis of flame retardant purity, and particularly relates to a rapid detection method and system for determining the purity of triphenyl phosphate. BACKGROUND

[0002] As a core additive component of engineering plastics, electronic packaging and halogen-free flame retardants, the purity of triphenyl phosphate directly determines the flame retardant efficiency, mechanical properties and long-term thermal stability of the end product. However, the existing detection process generally takes 3-4 hours, and is heavily dependent on the experience of the operator, resulting in a purity difference of up to 3-5% when the same batch of samples are measured in different laboratories on different dates, which cannot meet the requirements of high-end customers for impurity control and batch consistency.

[0003] Although a small number of automatic samplers or dilution platforms have appeared in existing detection technologies, there is still a lack of a full closed-loop system from sample pretreatment to result determination. Most high-performance liquid chromatographs only output raw spectra, and analysts need to export data offline, manually fit standard curves, calculate dilution factors, and fill out paper records. The entire process is fragmented, cannot be directly connected to an information system, and cannot be judged in real time whether the current analysis meets the reliable accuracy.

[0004] In terms of chromatographic peak recognition and quantitative algorithm, existing detection technologies generally use fixed slope thresholds or simple first derivative methods to find peak starting points. When the gradient elution baseline drifts, it is easy to cause false cutting or missing peaks, and it is also difficult to distinguish co-eluting impurities, resulting in a false high apparent purity. Although laboratories can perform offline comparison through DAD spectral libraries, they still need to manually export data, select reference spectra, and calculate similarity coefficients, which is time-consuming and has high professional threshold, and is difficult to replicate on site. SUMMARY

[0005] The present application aims to solve the problems in the prior art and provides a rapid detection method and system for determining the purity of triphenyl phosphate.

[0006] To achieve the above-mentioned purpose, the present application adopts the following technical scheme: a rapid detection method and system for determining the purity of triphenyl phosphate, comprising the following steps:

[0007] Step S1: obtaining a sample of triphenyl phosphate to be measured and injecting the sample into a sample pretreatment module of a rapid detection system;

[0008] Step S2: dissolving, filtering and constant-volume of the sample by the sample pretreatment module to obtain a pretreated sample solution;

[0009] Step S3: stepwise dilution of the pretreated sample solution to obtain a diluted sample solution;

[0010] Step S4, the rapid detection system calls the preset separation condition parameter, drives the high performance liquid chromatograph to separate the diluted sample solution, and generates a multi-wavelength chromatographic data stream;

[0011] Step S5, the multi-wavelength chromatographic data stream is subjected to real-time peak identification to obtain a separation spectrum, and the sample peak area is calculated;

[0012] Step S6, according to the sample peak area and the preset standard solution concentration-peak area model, the sample purity initial value is calculated;

[0013] Step S7, the sample is subjected to cyclic detection, the relative standard deviation of the sample purity initial value is calculated for multiple times, and the sample purity value passing the detection is output;

[0014] Step S8, the separation spectrum, the sample purity value and the sample batch number are packaged to generate a detection record.

[0015] The technical scheme provided by the application has at least the following beneficial effects:

[0016] The application can compress the sample detection period of triphenyl phosphate to less than 15 minutes through full-automatic process design, and through the cooperation of the intelligent sampling arm and the high-precision metering pump, the problems of uneven particle size of manual grinding, liquid transfer and constant volume visual deviation are fundamentally eliminated, the system is provided with a nitrogen protection conveying channel, a constant temperature dilution cavity and a sealed circulation loop, the seasonal drift of sample detection is solved, and the external arbitration and return cost of enterprises are effectively reduced.

[0017] In terms of data reliability, the application initiates a cyclic self-verification mechanism, compares the relative standard deviation of the latest group of purity values through a continuous three-time independent sampling-chromatography-computation process, and only when the relative standard deviation is less than or equal to 1% and the purity values in the group are within 90%-110% of the average value of the group, the sample is automatically locked and released, otherwise the cycle continues to the 10th time and an abnormal alarm is triggered, and the strategy makes each detection result have a statistical reliability label, which significantly improves the reliability of quality control compared with manual sampling.

[0018] In terms of compliance and informatization, the application automatically generates an XML electronic record conforming to FDA 21 CFR Part 11, integrates SHA-256 check code and operator digital certificate signature, seamlessly connects enterprise ERP, MES and customs declaration platform through LIMS, effectively shortens the delivery cycle of export orders, and significantly improves the international reputation of the brand.

[0019] From the economic benefits and green manufacturing point of view, the five-point external standard curve in the application can be used continuously for 30 days, reducing the consumption of standard products and waste liquid discharge, the gradient elution program significantly reduces the acetonitrile consumption, saves the organic solvent procurement and waste liquid disposal cost, the 15min rapid detection releases effectively reduce the warehouse inventory, the high consistency data provides accurate feedback for process optimization, the system modular design supports multi-channel parallel expansion and integration, and sets a green detection benchmark with small space, large capacity and zero emission for the industry. BRIEF DESCRIPTION OF DRAWINGS

[0020] In order to more clearly illustrate the technical solutions and advantages of the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiment or prior art description. Obviously, the drawings in the following description are only some embodiments of the present application, and for those skilled in the art, other drawings can also be obtained without creative labor.

[0021] Figure 1 The method flowchart provided for the embodiments of the present application;

[0022] Figure 2 The system structure diagram provided for the embodiments of the present application. DETAILED DESCRIPTION

[0023] In order to further illustrate the technical means and effects adopted by the present application to achieve the predetermined invention purpose, the following will combine the drawings and the preferred embodiments to specifically describe the specific implementation, structure, features and effects of the phosphorus acid triphenyl ester purity fixed value rapid detection method and system according to the present application. In the following description, different "one embodiment" or "another embodiment" do not necessarily refer to the same embodiment. In addition, the specific features, structures or characteristics in one or more embodiments can be combined in any suitable form.

[0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present application belongs.

[0025] The following embodiments are for illustrative purposes only, and are not intended to limit the scope of the present application.

[0026] The following will specifically describe the specific scheme of the phosphorus acid triphenyl ester purity fixed value rapid detection method and system provided by the present application in combination with the drawings.

[0027] Please refer to Figure 1 , which shows the method flowchart of the phosphorus acid triphenyl ester purity fixed value rapid detection method provided by one embodiment of the present application, and the method comprises the following steps:

[0028] Step S1, obtain the sample of the triphenyl phosphate to be tested, and inject it into the sample pretreatment module of the rapid detection system;

[0029] In step S1, the following substeps are further included:

[0030] S1-1, according to GB / T 6679, sample multiple points of the same batch of triphenyl phosphate to be tested, combine the samples, and further divide them by quartering to obtain the sample;

[0031] S1-2, grind the sample in a mortar to a particle size of ≤0.5 mm, further weigh 1.0000 g ± 0.0002 g of the ground sample with a 0.1 mg precision analytical balance, and transfer it to a special sample bottle;

[0032] S1-3, register the special sample bottle containing the ground sample by scanning code recognition method and bind the batch number;

[0033] S1-4, under nitrogen protection, the ground sample is transported to the pretreatment module at a constant flow rate of 0.5-1.0 mL / min within 30-60 seconds.

[0034] It should be noted that GB / T 6679 provides that: the full name is National Standard GB / T 6679 General Rules for Sampling of Solid Chemical Products, which is a unified provision for the multi-point sampling amount, sampler type, sample label and safety requirements of bagged, barreled and other solid commodities. According to this standard, multi-point sampling + combined division can ensure that the sampled triphenyl phosphate sample is representative of the batch, and avoid distortion of the subsequent purity results due to sampling deviation.

[0035] Quartering division: after the combined original sample is stacked into a cone and flattened into a round cake, it is divided into four equal parts vertically with a cross plate, and the diagonally opposite two parts are taken and mixed again. Repeat until the remaining amount meets the detection requirement. This method can quickly reduce the kilogram level to the gram level without weighing and counting, and the division process does not introduce particle size or component segregation, maintaining the representativeness of the sample.

[0036] Analytical balance: used to compress the weighing error of the divided sample to within 0.02% to ensure that the uncertainty of the weighing item is not introduced in the subsequent purity calculation.

[0037] Special sample bottle: 20 mL brown threaded glass bottle with inert material, RFID / two-dimensional code label and tamper-proof seal, used to realize one-to-one binding of sample-bottle code-batch number, ensure traceability throughout the subsequent steps, avoid batch confusion or cross contamination.

[0038] Step S2, the sample pretreatment module dissolves, filters and constant volumes the sample to obtain a pretreated sample solution;

[0039] wherein in step S2, further comprising the following sub-steps:

[0040] S2-1, warming the dissolution cavity of the pretreatment module to 45±2℃ at a rate of 5℃ / min, mixing the ground sample with acetonitrile-water dilution solvent at a volume ratio of 1:4 and injecting into the dissolution cavity, starting magnetic stirring, and uniformly mixing at a speed of 800 rpm for 5 min to obtain an initial solution;

[0041] S2-2, filtering the initial solution through a 0.22 μm polytetrafluoroethylene needle filter, controlling the filtering pressure at 0.2 MPa, and transferring the filtered solution to a constant-temperature constant-volume cavity, cooling to 25±0.5℃ at a rate of 0.3℃ / min and maintaining for 10 min;

[0042] S2-3, supplementing acetonitrile-water dilution solvent into the constant-temperature constant-volume cavity to constant volume using a high-precision metering pump until the liquid level reaches the 25 mL constant-volume scale, and continuously stirring at a low speed of 200 rpm during the constant-volume process;

[0043] S2-4, circulating the constant-volume solution at 25±0.5℃ through a sealed circulation loop for 2 min to obtain a pretreated sample solution.

[0044] It should be noted that the acetonitrile-water dilution solvent: an isocratic diluent obtained by mixing chromatographically pure acetonitrile and ultrapure water at a volume ratio of 4:1, used for rapidly dissolving the sample of the phosphoric acid triphenyl ester to be tested at 45℃, has high solubility for phosphoric acid triphenyl ester, is compatible with its liquid phase gradient, and can effectively eliminate the solvent effect peak after injection.

[0045] Magnetic stirring: specifically, using a rotating magnetic field to drive a polytetrafluoroethylene magnet to stir without contact, with a speed of 200-800 rpm adjustable, suitable for sealed cavities, used to provide uniform turbulent flow during the warming and constant-volume stages, ensure uniform solution concentration, shorten the dissolution equilibrium time, and prevent local supersaturation.

[0046] Polytetrafluoroethylene needle filter: an organic phase / water phase universal filter with a pore size of 0.22 µm, capable of trapping bacteria and insoluble particles ≥0.22 µm, used to remove packaging debris, dust, and unsolved microcrystals that may be introduced during grinding, protecting the chromatographic column from being clogged while reducing background impurity peaks.

[0047] Constant-temperature constant-volume cavity: a double-layer Peltier temperature-controlled cavity with a temperature control accuracy of ±0.1℃, with a 25 mL laser scale line on the top of the cavity, used for constant-volume at 25℃ to eliminate the volume error caused by thermal expansion.

[0048] High-precision metering pump: a ceramic plunger micropump with a resolution of 0.1 µL and a repeatability CV ≤ 0.05 %, which can be real-time volume compensated by closed-loop grating feedback, used to slowly supplement the constant-temperature constant-volume cavity with 0.5–1.0 mL / min to the scale to avoid liquid surface overshoot and bubble entrainment.

[0049] Sealed circulation loop: a closed-loop flow path composed of a PTFE capillary, a magnetic gear pump, and a one-way valve, which can complete 10 times the cavity volume circulation within 2 min, used to further homogenize the solution and eliminate concentration gradients while keeping the system closed after the constant-volume endpoint, preventing concentration drift caused by acetonitrile evaporation.

[0050] Step S3, the pretreated sample solution is diluted step by step to obtain a diluted sample solution;

[0051] In step S3, the following substeps are further included:

[0052] S3-1, 5.00 mL of the pretreated sample solution is removed by the intelligent sampling arm, mixed with 20.0 mL of acetonitrile-water dilution solvent, and injected into a constant-temperature primary dilution cavity at 25°C, and magnetic stirring is started, with a stirring speed of 300 rpm for 30 s to obtain a primary dilution solution;

[0053] S3-2, 2.00 mL of the primary dilution solution is transferred to a constant-temperature secondary dilution cavity at 25°C by the intelligent sampling arm, and 18.0 mL of the above-mentioned acetonitrile-water dilution solvent is added, and magnetic stirring is started, with a stirring speed of 400 rpm for 45 s to obtain a secondary dilution solution;

[0054] S3-3, the secondary dilution solution is filtered through a 0.22 µm polytetrafluoroethylene needle filter to obtain a diluted sample solution.

[0055] It should be noted that the intelligent sampling arm: a six-axis micro-SCARA mechanical arm integrating a closed-loop stepper motor with a positioning accuracy of ± 0.01 mm and a disposable PTFE sampling needle, embedded with RFID identification and liquid level sensing to correct the needle depth in real time and prevent air suction or needle collision, which receives host commands through CAN bus, automatically completes two-stage pipetting of 5.00 mL and 2.00 mL, automatically inserts the cleaning station after sampling to flush the inner and outer walls with acetonitrile-water to avoid cross contamination, and the whole process does not require manual intervention, ensuring the accuracy of the volume and the consistency of the beat of the step-by-step dilution, providing a particle-free and concentration-accurate diluted sample solution for the subsequent liquid chromatography analysis.

[0056] Step S4, the pre-set separation condition parameters are called by the rapid detection system, and the high-performance liquid chromatograph is driven to separate the diluted sample solution to generate a multi-wavelength chromatographic data stream;

[0057] In step S4, the following substeps are further included:

[0058] S4-1, The rapid detection system reads the preset separation condition parameters from the local database and encapsulates the separation condition parameters into an instruction package, which is sent to the high-performance liquid chromatograph through LAN to automatically complete column balancing and baseline stability verification.

[0059] S4-2, 10 μL of the diluted sample solution is moved by the sample needle and input into the high-performance liquid chromatograph for gradient elution. During the gradient elution process, the diode array detector synchronously collects absorption signals at 210 nm, 254 nm and 280 nm three channels at a frequency of 20 Hz to generate a multi-wavelength chromatographic data stream in real time.

[0060] S4-3, After the gradient elution is completed, the rapid detection system packages the multi-wavelength chromatographic data stream into a RAW file for caching, and immediately triggers a real-time peak recognition algorithm.

[0061] It should be noted that the local database: the SQLite embedded database built-in the rapid detection system can pre-store more than 50 sets of separation condition parameters including phosphoric acid triphenyl ester special gradient, flow rate, column temperature and wavelength. The parameters are stored in JSON format and can be queried and called within 0.2 seconds, supporting offline delivery, version management and automatic backup.

[0062] The preset separation condition parameter example is as follows:

[0063]

[0064] LAN: 100M Ethernet using Modbus-TCP protocol, delay ≤2ms, supporting remote start and stop and fault alarm, used for real-time delivery of instruction package and reception of baseline noise, pressure and other state frames, realizing high-speed bidirectional communication between the system and the high-performance liquid chromatograph without frame loss.

[0065] High-performance liquid chromatograph: equipped with a 120-position automatic sampler and a four-element low-pressure gradient pump, with a built-in degassing machine and a column oven, pressure resistance 60MPa, flow rate accuracy ±0.5%, sample repeatability ≤0.3%, which can automatically complete degassing, column balancing and baseline stability verification through external instructions, ensuring stable TPP gradient elution and accurate quantification.

[0066] Gradient elution: continuously changing the composition of the mobile phase according to the preset curve within 12 min, so that TPP and polar impurities are eluted in turn; compared with isocratic mode, gradient can shorten the analysis time by 40%, reduce peak broadening and column residue, while ensuring the separation degree of each component ≥1.8, meeting the requirements of rapid purity screening and impurity synchronous detection.

[0067] Diode array detector: sampling frequency 20 Hz, full spectrum collection from 190 to 800 nm, and absorption signals can be output simultaneously at three channels of 210, 254 and 280 nm to provide multi-dimensional data for TPP main peak quantification and impurity determination.

[0068] RAW: a binary data file for saving metadata containing time-absorbance matrix, wavelength and method, which can directly trigger peak identification algorithm after caching, avoid information loss caused by format conversion, support subsequent audit tracking and offline reprocessing, and meet the requirements of FDA 21 CFR Part 11 electronic records.

[0069] Step S5, real-time peak identification of the multi-wavelength chromatographic data stream to obtain a separation spectrum, and calculation of sample peak area;

[0070] In step S5, the following sub-steps are further included:

[0071] S5-1, the rapid detection system performs Savitzky-Golay 9-point smoothing filtering on the absorption signals at three channels of 210 nm, 254 nm and 280 nm in the multi-wavelength chromatographic data stream, respectively, to obtain filtered absorption signals;

[0072] S5-2, setting the peak starting point slope threshold to 0.3 mAU / min, and detecting the peak starting point and falling point in the filtered absorption signals by the first derivative + sliding window algorithm, further taking the 210 nm channel as the main channel and the 254 nm and 280 nm channels as the auxiliary channels, calculating the peak purity by the spectral similarity method, and determining it as a single component when the peak purity is greater than or equal to 0.999, to obtain a separation spectrum containing the main peak of triphenyl phosphate and impurity peaks;

[0073] S5-3, baseline automatic correction of the main peak by linear interpolation method to obtain sample peak area and retention time.

[0074] It should be noted that the Savitzky-Golay 9-point smoothing filtering is a three-order least squares polynomial fitting within 9 consecutive data, which replaces the original absorbance with the fitted value to eliminate random noise under the premise of preserving the authenticity of peak area, avoids peak broadening caused by traditional moving average, and makes the subsequent derivative calculation stable and repeatable, providing a high signal-to-noise ratio data basis for the peak starting point / falling point discrimination of the 0.3 mAU / min slope threshold.

[0075] First derivative + sliding window algorithm: the first derivative of the smoothed signal is calculated within a 5-point window and the derivative curve is output in real time. When the calculated derivative value is higher than 0.3 mAU / min for 3 consecutive points, the peak start point is marked. When the calculated derivative value is lower than -0.3 mAU / min, the peak end point is marked. The window automatically shifts with the baseline drift. This algorithm can resist slow background drift caused by gradient elution and achieve online peak detection with a delay of less than 0.5 s.

[0076] Spectral similarity method: the normalized spectral vector within ±5 points of the peak top of the 210 nm main channel is calculated with the cosine similarity of the normalized spectral vector of the corresponding interval of the 254 nm and 280 nm auxiliary channels. If the similarity is ≥0.999, it is determined to be a single component, otherwise it is marked as a co-eluted impurity. This method does not require the use of spectral library to verify the purity of the peak online and ensures that the main peak of triphenyl phosphate is not masked by impurity peaks.

[0077] Linear interpolation method: 3 points before the detected peak start point and 3 points after the peak end point are taken to form a local baseline, and the background is deducted from each data point in the peak through the baseline equation to eliminate the peak bottom tilt caused by gradient drift. This method can accurately restore the true peak area, has small calculation amount and strong real-time performance, and ensures that the purity quantitative error is less than 0.5%.

[0078] Step S6, according to the sample peak area and the pre-set standard solution concentration-peak area model, the sample purity initial value is calculated;

[0079] In step S6, the following sub-steps are further included:

[0080] S6-1, the rapid detection system calls the triphenyl phosphate standard curve equation established by the 5-point external standard method from the local database, and substitutes the sample peak area to calculate the concentration of the diluted sample solution, and the formula is as follows:

[0081]

[0082] In the formula, The concentration of the diluted sample solution (unit: mg / mL) is the concentration of the diluted sample solution, The sample peak area is the sample peak area, and k and b are constants locked by the 5-point external standard method;

[0083] S6-2, further according to the total dilution multiple D=50, the concentration of the pretreated sample solution is automatically calculated, and the formula is as follows:

[0084]

[0085] In the formula, The concentration of the pretreated sample solution (unit: mg / mL) is the concentration of the pretreated sample solution, and D is the total dilution multiple;

[0086] S6-3, read the sample mass m = 1.0 g in the weighing record and the constant volume V = 25 mL, and calculate the initial sample purity according to the following formula:

[0087]

[0088] wherein, is the initial sample purity, (unit: mL) is the constant volume, (unit: mg) is the sample mass.

[0089] It should be noted that the 5-point external standard method: take 25 mg of triphenyl phosphate standard (which can be purchased without separate configuration), dissolve it with acetonitrile-water diluent and dilute it step by step to 0.2, 0.5, 1.0, 2.0 and 4.0 (mg / mL) five concentrations, each 3 times, and perform liquid chromatography determination under the same gradient, wavelength and injection volume as the sample. The average peak area A is linearly regressed with the concentration C to obtain the external standard curve equation C = kA + b. This method can offset the daily response drift of the instrument. Once the slope k and the intercept b are locked, they are stored in the local database. The sample only needs to measure the peak area to directly calculate the concentration, which is simple, fast and meets the rapid screening requirements.

[0090] Total dilution factor: the sample in this method is first diluted by "5 mL to 25 mL" in the first stage, and then diluted by "2 mL to 20 mL" in the second stage. The total dilution factor D = (25 / 5) x (20 / 2) = 50. The concentration of the diluted solution is measured , and multiplied by 50 to calculate the original pretreatment solution concentration , and substitute the sample mass and the constant volume to obtain the initial purity , the sensitivity and linear range are considered throughout the whole process, and no additional calibration is required.

[0091] Step S7, cyclically detect the sample, calculate the relative standard deviation of the initial purity of multiple samples, and output the sample purity value that passes the detection;

[0092] In step S7, the following sub-steps are also included:

[0093] S7-1, cyclically sample and purity detection for the same batch of pretreated sample solution, and continuously obtain the initial sample purity multiple times (i), wherein ;

[0094] S7-2, calculate the relative standard deviation of the (i) of the last three detections immediately after obtaining a new (i-2), (i-1) and (i).

[0095] S7-3, if and only if the relative standard deviation calculated for three consecutive times is ≤1% and (i-2), (i-1), and (i) are all within 90%-110% of the mean of the three, it is determined that the detection accuracy meets the standard, and the rapid detection system automatically terminates the sampling-purity detection cycle and (i-2), (i-1), and (i) are all within 90%-110% of the mean of the three, it is determined that the detection accuracy meets the standard, and the rapid detection system automatically terminates the sampling-purity detection cycle and

[0096] S7-4, if the detection accuracy does not meet the standard for 10 consecutive cycles, the rapid detection system triggers an abnormal alarm, automatically suspends the sampling-purity detection cycle, and prompts to recheck the chromatographic conditions or prepare a new sample.

[0097] It should be noted that the sampling-purity detection cycle

[0098] Step S8, packaging the separation spectrum, sample purity value, and sample batch number to generate a detection record;

[0099] In step S8, the following sub-steps are also included:

[0100] S8-1, the rapid detection system automatically captures the separation spectrum, sample purity value, and corresponding sample batch number of the same batch of samples, writes them into an XML template conforming to the FDA 21 CFR Part 11 electronic record standard, and automatically attaches a timestamp, instrument serial number, and operator digital certificate signature to generate a detection record, then calculates its SHA-256 checksum and writes it into the XML file;

[0101] S8-2, upload the XML format detection record to the cloud database for archiving through LIMS, and further generate a PDF format copy according to the detection record for on-site printing and manual review;

[0102] S8-3, the rapid detection system performs RSA encryption and local backup on the XML format detection record.

[0103] It should be noted that the FDA 21 CFR Part 11 electronic record standard: a core regulation on electronic records and electronic signatures issued by the FDA, including main clauses such as system verification, audit tracking, permission control, electronic signature, and original record preservation. The present application uses an XML template conforming to this standard to ensure that the detection record can be used as a legal inspection basis without paper verification, meeting domestic and international audit requirements.

[0104] SHA-256 check code: a kind of cryptographic hash function, can generate 256-bit unique fingerprint for any length input, system generates XML format detection record after, it is carried out SHA-256 operation to its full text, obtains 64-bit hexadecimal check code and is written into same record file, this method can quickly identify data tampering, realizes low cost, high efficiency integrity verification, provides credible evidence for audit tracking.

[0105] RSA encryption: a kind of non-symmetrical encryption algorithm based on key pair, system uses server private key to sign XML record, then uses operator local private key to encrypt twice, generates encrypted package and stores in local NAS, simultaneously public key is uploaded to LIMS, any third party can use public key to decrypt and verify source and integrity, prevent record from being counterfeited or leaked, can satisfy long-term secure archiving requirements of electronic record.

[0106] Please refer to Figure 2 , it shows the system structure diagram of a kind of phosphorus acid triphenyl ester purity fast detection system provided by one embodiment of the application, the system includes:

[0107] Sample collection module: for obtaining the sample of phosphorus acid triphenyl ester to be measured, and injecting the pretreatment module of fast detection system;

[0108] Sample pretreatment module: for dissolving, filtering and constant-volume of sample, to obtain pretreated sample solution;

[0109] Sample dilution module: for step-by-step dilution of pretreated sample solution, to obtain dilute sample solution;

[0110] Liquid chromatography separation and identification module: for driving high performance liquid chromatograph to separate dilute sample solution by preset separation condition parameter, to generate multi-wavelength chromatography data stream, further to carry out real-time peak identification to the multi-wavelength chromatography data stream to obtain separation spectrum, and calculate sample peak area;

[0111] Sample purity calculation module: for calculating sample purity initial value according to sample peak area and preset standard solution concentration-peak area model;

[0112] Deviation detection module: for cyclic detection of sample, and calculate the relative standard deviation of multiple sample purity initial values, and output the sample purity value passed through detection;

[0113] Record generation module: separation spectrum, sample purity value and sample batch number are packaged to generate detection record.

[0114] The above-described embodiments are only used to illustrate the technical solutions of the present application, but not limit them; although the present application is described in detail with reference to the foregoing embodiments, those skilled in the art should understand that: it can still modify the technical solutions recorded in the foregoing embodiments, or make equivalent replacement to part of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application, and should be included in the protection scope of the present application.

Claims

1. A rapid method for determining the purity of triphenyl phosphate, characterized in that, The method includes: Step S1: Obtain the sample of triphenyl phosphate to be tested and inject it into the sample pretreatment module of the rapid detection system; In step S2, the sample pretreatment module dissolves, filters, and adjusts the volume of the sample to obtain a pretreated sample solution. Step S3: The pretreated sample solution is serially diluted to obtain a diluted sample solution; Step S4: The rapid detection system calls the preset separation condition parameters and drives the high-performance liquid chromatograph to separate the diluted sample solution and generate a multi-wavelength chromatographic data stream. Step S5: Real-time peak identification is performed on the multi-wavelength chromatographic data stream to obtain the separation spectrum, and the peak area of ​​the sample is calculated; Step S6: Calculate the initial value of sample purity based on the sample peak area and the pre-set standard solution concentration-peak area model. Step S7: Perform cyclic testing on the sample, calculate the relative standard deviation of the initial sample purity values ​​multiple times, and output the purity value of the sample that passes the test. Step S8: Package the separation spectrum, sample purity value, and sample batch number to generate a test record; Step S2 further includes the following sub-steps: S2-1, heat to 45±2℃ at 5℃ / min, mix the ground sample with acetonitrile-water dilution solvent at a volume ratio of 1:4, pour into the dissolution chamber, stir magnetically at 800rpm, mix for 5min to obtain the initial solution; S2-2, filtered through a 0.22μm polytetrafluoroethylene needle filter at a pressure of ≤0.2MPa, the filtrate was transferred into a constant temperature and volume chamber, cooled to 25±0.5℃ at 0.3℃ / min and held at that temperature for 10min; S2-3, use a high-precision metering pump to add acetonitrile-water to dilute the solvent to the 25mL mark, and stir at 200rpm during the volume adjustment process; S2-4, through a sealed circulation loop, is kept at a constant temperature of 25±0.5℃ for 2 minutes to obtain a pretreated sample solution; Step S3 further includes the following sub-steps: S3-1: 5.00 mL of pretreated sample is transferred through the intelligent injection arm and mixed with 20.0 mL of acetonitrile-water dilution solvent. The mixture is then injected into the 25°C constant temperature primary dilution chamber, magnetically stirred at 300 rpm, and homogenized for 30 s to obtain the primary dilution solution. S3-2, 2.00 mL of primary diluent is transferred to the 25℃ constant temperature secondary dilution chamber through the intelligent injection arm, 18.0 mL of diluent is added, and the mixture is stirred magnetically at 400 rpm for 45 s to obtain the secondary diluent; S3-3, after filtering the secondary dilution solution through a 0.22µm polytetrafluoroethylene needle filter, a diluted sample solution is obtained; Step S7 further includes the following sub-steps: S7-1, cyclically sample and test the purity of the same batch of pretreated sample solutions, obtaining initial purity values ​​multiple times. (i), where ; S7-2, each time a new one is obtained (i) Immediately calculate the results of the three most recent tests. (i-2) (i-1) and (i) relative standard deviation; S7-3, if and only if the relative standard deviation of three consecutive calculations is ≤1% and (i-2) (i-1) and (i) When all three values ​​are within 90% to 110% of their average, the detection accuracy is deemed satisfactory, and the rapid detection system automatically terminates the sampling-purity detection cycle. (i-2) (i-1) and The mean of (i) is used as the final sample purity value; S7-4 If the standard is not met after 10 consecutive cycles, the system will trigger an abnormal alarm, automatically suspend sampling and purity detection, and prompt the user to check the chromatographic conditions or prepare the sample again.

2. The rapid detection method for determining the purity of triphenyl phosphate according to claim 1, characterized in that: Step S1 further includes the following sub-steps: S1-1: Multiple samples of triphenyl phosphate to be tested from the same batch were taken, combined, and then reduced to fractions using the quartering method to obtain the sample. S1-2, grind the sample to a particle size ≤0.5mm, weigh 1.0000g±0.0002g, and transfer it into a special sample bottle; S1-3, Register the sample bottle and bind the batch number by scanning the code; S1-4, under nitrogen protection, the ground sample is delivered to the pretreatment module at a flow rate of 0.5–1.0 mL / min within 30–60 s.

3. The rapid detection method for determining the purity of triphenyl phosphate according to claim 1, characterized in that: Step S4 further includes the following sub-steps: S4-1, the rapid detection system reads separation condition parameters from the local database, encapsulates them into an instruction packet, and sends it to the high performance liquid chromatograph via LAN to automatically complete column equilibration and baseline verification; S4-2: The injection needle transfers 10µL of diluted sample solution, which is then subjected to gradient elution by high performance liquid chromatography; the diode array detector acquires absorption signals at 20Hz in three channels at 210nm, 254nm and 280nm, and generates multi-wavelength chromatographic data streams in real time. S4-3 After elution, the system packages the data stream into a RAW file cache and triggers the real-time peak recognition algorithm.

4. The rapid detection method for determining the purity of triphenyl phosphate according to claim 1, characterized in that: Step S5 further includes the following sub-steps: S5-1, the rapid detection system performs Savitzky-Golay 9-point smoothing filtering on the three-channel absorption signals of 210nm, 254nm and 280nm to obtain the filtered signal; S5-2, with a peak initiation slope threshold of 0.3 mAU / min, the peak initiation and termination points are detected using the first derivative + sliding window algorithm; the 210 nm channel is the main channel, with 254 nm and 280 nm as auxiliary channels, and the peak purity is calculated by spectral similarity. When the purity is ≥0.999, it is determined to be a single component, and the separation spectrum of the main peak containing triphenyl phosphate and impurity peaks is obtained. S5-3, perform linear interpolation baseline correction on the main peak to obtain the sample peak area and retention time.

5. The rapid detection method for determining the purity of triphenyl phosphate according to claim 1, characterized in that: Step S6 further includes the following sub-steps: S6-1, the rapid detection system retrieves the triphenyl phosphate standard curve equation established using the 5-point external standard method from the local database, substitutes it into the sample peak area, and calculates the concentration of the diluted sample solution using the following formula: ； In the formula, (Unit: mg / mL) represents the concentration of the diluted sample solution. Here, is the peak area of ​​the sample, and k and b are constants locked by the 5-point external standard method; S6-2, further, automatically recalculate the concentration of the pretreated sample solution based on the overall dilution factor D=50, using the following formula: ； In the formula, (Unit: mg / mL) represents the concentration of the pretreated sample solution, and D represents the overall dilution factor; S6-3, read the sample mass m=1.0g and the final volume V=25mL from the weighing record, and calculate the initial value of sample purity according to the following formula: ； In the formula, This is the initial value for sample purity. (Unit: mL) is the constant volume. (Unit: mg) represents the sample mass.

6. The rapid detection method for determining the purity of triphenyl phosphate according to claim 1, characterized in that: Step S8 further includes the following sub-steps: S8-1, the rapid detection system captures the separation spectrum, purity value and batch number of samples from the same batch, writes them into an XML template that conforms to the FDA 21CFR Part 11 standard, and adds timestamps, instrument serial numbers and operator digital signatures. After generating the detection record, it calculates the SHA-256 checksum and writes it into the file. S8-2 uploads XML detection records to a cloud database for archiving via LIMS and generates PDF copies for printing and manual review; S8-3, the rapid detection system encrypts XML detection records with RSA and backs them up locally.

7. A rapid detection system for determining the purity of triphenyl phosphate used in the rapid detection method for determining the purity of triphenyl phosphate according to claim 1, characterized in that, The system includes: Sample acquisition module: Acquires the triphenyl phosphate sample to be tested and injects it into the pretreatment module; Sample pretreatment module: Dissolves, filters, and maintains constant temperature and volume to obtain a pretreatment solution; Sample dilution module: Dilutes the pretreatment solution stepwise to obtain a diluted sample solution; Liquid chromatography separation and identification module: Drives the high-performance liquid chromatograph to separate samples according to preset conditions, generates multi-wavelength data streams, identifies peaks in real time to generate separation chromatograms, and calculates peak areas; Sample purity calculation module: Calculates the initial value of sample purity based on the standard solution concentration-peak area model; Deviation detection module: performs cyclic testing on the sample, calculates the relative standard deviation of the initial purity value, and outputs a qualified purity value; Record generation module: Packages the separation spectrum, purity value and batch number to generate a test record.

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