In the pharmaceutical industry, the quality control of pharmaceutical water and water for injection is related to human life and health. Therefore, the pharmaceutical industry has special requirements for the detection and monitoring of total organic carbon. Online monitoring can accurately and real-time feedback the total organic carbon content in pharmaceutical water. It can provide data protection for safe and efficient pharmaceutical production, so TOC online monitor is an essential instrument for most pharmaceutical companies.

The 2015 edition of the Chinese Pharmacopoeia stipulates that the total organic carbon content of pharmaceutical water should not exceed 0.50mg/L, the equipment used should be calibrated, and the system applicability of the equipment should be tested regularly with standard solutions in accordance with the prescribed method. According to this regulation, we selected TOC-1700 total organic carbon analyzer to monitor the total organic carbon of ultrapure water. This instrument can test the organic carbon content of pure water, deionized water for the pharmaceutical industry and water for injection, and can detect the semiconductor industry The TOC content in ultra-pure water such as power plants, scientific research units, laboratories, etc. can be used to verify the cleaning effect in the cleaning verification process in the pharmaceutical and biochemical fields. It can also be used in the water system of the pharmaceutical industry and the ultra-pure water in the semiconductor industry. On-line monitoring of the total organic carbon content of ultrapure water in the preparation system and wafer process, and the preparation of deionized water from power plants.

According to the requirements of the 2015 edition of the Chinese Pharmacopoeia, the TOC-1700 total organic carbon analyzer is first calibrated, and then the system suitability test of the instrument is performed, and finally the ultrapure water preparation equipment is connected to monitor the water production effect of the equipment .

1. Experiment preparation:

1. Experimental equipment:

- TOC-1700 total organic carbon analyzer, manufactured by Shanghai Metash Instrument Co., Ltd.

- Ultrapure water preparation system

2. Reagent preparation

(1) Water for inspection: conductivity<1.0µS/cm and TOC<100ppb

(2) Sucrose: reference substance or purity standard substance

(3) 1,4-P-benzoquinone: reference substance or standard reagent

3. Preparation of the solution

1) Sucrose standard stock solution: accurately weigh 120mg of the sucrose reference substance dried to constant weight at 105℃, dissolve it in ultrapure water, transfer it into a 1000mL volumetric flask, dilute with ultrapure water to the mark, and mix. The organic carbon concentration of this solution is 50mg/L, and it is stored as a standard stock solution. Other concentrations of stock solutions can also be prepared according to relevant calculations.

2) Sucrose standard solution: Use a 2mL single-line pipette to accurately transfer 2mL sucrose standard stock solution into a 500mL volumetric flask, dilute with ultrapure water to the standard line, and mix. The concentration of organic carbon in this solution is 200μg/L; a 10mL single-marked pipette accurately transfers 10mL of sucrose standard stock solution to a 1000mL volumetric flask, dilutes to the mark with ultrapure water, and mixes. The concentration of organic carbon in this solution is 500μg/L; a 10mL single-marked pipette accurately transfers 10mL of sucrose standard stock solution to a 500mL volumetric flask, dilutes to the mark with ultrapure water, and mixes. The concentration of organic carbon in this solution is 1000 μg/L.

3) 1.4-p-benzoquinone standard stock solution: accurately weigh 150mg of 1.4-p-benzoquinone reference substance, dissolve it in ultrapure water, transfer it into a 1000mL volumetric flask, dilute with ultrapure water to the standard line, and mix. The organic carbon concentration of this solution is 100mg/L, and it is stored as a standard stock solution.

4) 1.4-P-benzoquinone standard liquid: Use a 5mL single-marked pipette to accurately pipette 5mL 1.4-p-benzoquinone standard stock solution into a 1000mL volumetric flask, dilute to the mark with ultrapure water, and mix. The concentration of organic carbon in this solution is 500μg/L.

2. Instrument calibration

In accordance with the calibration process of "TOC-1700 Total Organic Carbon Analyzer Standard Operating Procedure", test the response of the inspection water, the total organic carbon content of 200μg/L, 500μg/L, and 1000μg/L calibration solution. The instrument automatically calculates the zero point compensation value and Calibration constant; input the obtained calibration parameters into the instrument system settings, save, and the instrument can test samples.

3. System suitability verification

In accordance with the "TOC-1700 Total Organic Carbon Analyzer Standard Operating Procedure" test, the response values of inspection water, 500μg/L sucrose solution, and 500μg/L 1,4-quinone solution were obtained respectively.

Calculate the system suitability of the instrument according to the following formula;

Calculation formula: Response efficiency% = 100 [(rss-rw)/(rs-rw)]

In the formula:

rw—— the response average value of total organic carbon check water;

rs—— the average response of 500μg/L sucrose solution;

rss—— the average response of 500μg/L 1,4-quinone solution

According to the measured response efficiencies of the instrument, the formula is calculated to get

Response efficiency% = 100[(492.1—11.0)/(518.7—11.0)]=94.8%

The 2015 version of the Chinese Pharmacopoeia requires that the response efficiency expressed as a percentage should be 85% to 115%.

The results show that the system applicability of TOC-1700 total organic carbon analyzer meets the requirements and can ensure the accuracy and precision of the sample test results.

4. Online monitoring

According to the installation instructions of "TOC-1700 Total Organic Carbon Analyzer Manual", connect the online interface board of the instrument to the circulating pipeline of the ultrapure water equipment, the ultrapure water equipment starts to take water and produce water, and the instrument continuously samples every 2 minutes Read the total organic carbon test data once, last for 1 hour, and get 30 test results.

From the data in the above table, it can be known that the ultrapure water equipment can remove most of the total organic carbon in the water within 10 minutes, and after about 30 minutes, the total organic carbon content of the ultrapure water reaches a relatively stable level.

5. Conclusion

The calibration and system applicability of the TOC-1700 total organic carbon analyzer are in compliance with the 2015 edition of the Chinese Pharmacopoeia. It can accurately test the total organic carbon content in ultra-pure water-grade purified water and pharmaceutical water. It can be used in ultra-pure water. Online monitoring of total organic carbon in pure water preparation equipment.