Non-ionic Cellulose Ether by Gas Chromatography

The content of substituents in non-ionic cellulose ether was determined by gas chromatography, and the results were compared with chemical titration in terms of time-consuming, operation, accuracy, repeatability, cost, etc., and the column temperature was discussed. The influence of chromatographic conditions such as column length on the separation effect. The results show that gas chromatography is an analytical method worth popularizing.
Key words: non-ionic cellulose ether; gas chromatography; substituent content

Nonionic cellulose ethers include methylcellulose (MC), hydroxypropylmethylcellulose (HPMC), hydroxyethylcellulose (HEC), etc. These materials are widely used in medicine, food, petroleum, etc. Since the content of substituents has a great influence on the performance of non-ionic cellulose ether materials, it is necessary to determine the content of substituents accurately and quickly. At present, most domestic manufacturers adopt the traditional chemical titration method for analysis, which is labor-intensive and difficult to guarantee accuracy and repeatability. For this reason, this paper studies the method of determining the content of non-ionic cellulose ether substituents by gas chromatography, analyzes the factors affecting the test results, and obtains good results.

1. Experiment
1.1 Instrument
GC-7800 gas chromatograph, produced by Beijing Purui Analytical Instrument Co., Ltd.
1.2 Reagents
Hydroxypropyl methylcellulose (HPMC), hydroxyethylcellulose (HEC), homemade; methyl iodide, ethyl iodide, isopropane iodide, hydroiodic acid (57%), toluene, adipic acid, o-di Toluene was of analytical grade.
1.3 Gas chromatography determination
1.3.1 Gas chromatography conditions
Stainless steel column ((SE-30, 3% Chmmosorb, WAW DMCS); vaporization chamber temperature 200°C; detector: TCD, 200°C; column temperature 100°C; carrier gas: H2, 40 mL/min.
1.3.2 Preparation of standard solution
(1) Preparation of internal standard solution: Take about 6.25g of toluene and place in a 250mL volumetric flask, dilute to the mark with o-xylene, shake well and set aside.
(2) Preparation of standard solution: different samples have corresponding standard solutions, and HPMC samples are taken as an example here. In a suitable vial, add a certain amount of adipic acid, 2 mL of hydroiodic acid and internal standard solution, and accurately weigh the vial. Add an appropriate amount of iodoisopropane, weigh it, and calculate the amount of iodoisopropane added. Add methyl iodide again, weigh equally, calculate the amount that adds methyl iodide. Vibrate fully, let it stand for stratification, and keep it away from light for later use.
1.3.3 Preparation of sample solution
Accurately weigh 0.065 g of dry HPMC sample into a 5 mL thick-walled reactor, add equal weight of adipic acid, 2 mL of internal standard solution and hydroiodic acid, quickly seal the reaction bottle, and accurately weigh it. Shake, and heat at 150°C for 60 minutes, shaking properly during the period. Cool and weigh. If the weight loss before and after the reaction is greater than 10 mg, the sample solution is invalid and the solution needs to be re-prepared. After the sample solution was allowed to stand for stratification, carefully draw 2 μL of the upper organic phase solution, inject it into the gas chromatograph, and record the spectrum. Other non-ionic cellulose ether samples were treated similarly to HPMC.
1.3.4 Measuring principle
Taking HPMC as an example, it is a cellulose alkyl hydroxyalkyl mixed ether, which is co-heated with hydroiodic acid to break all the methoxyl and hydroxypropoxyl ether bonds and generate the corresponding iodoalkane .
Under high temperature and airtight conditions, with adipic acid as a catalyst, HPMC reacts with hydroiodic acid, and methoxyl and hydroxypropoxyl are converted into methyl iodide and isopropane iodide. Using o-xylene as absorbent and solvent, the role of catalyst and absorbent is to promote the complete hydrolysis reaction. Toluene is selected as the internal standard solution, and methyl iodide and isopropane iodide are used as the standard solution. According to the peak areas of the internal standard and the standard solution, the content of methoxyl and hydroxypropoxyl in the sample can be calculated.

2. Results and discussion
The chromatographic column used in this experiment is non-polar. According to the boiling point of each component, the peak order is methyl iodide, isopropane iodide, toluene and o-xylene.
2.1 Comparison between gas chromatography and chemical titration
The determination of the methoxyl and hydroxypropoxyl content of HPMC by chemical titration is relatively mature, and currently there are two commonly used methods: the Pharmacopoeia method and the improved method. However, both of these two chemical methods require the preparation of a large amount of solutions, the operation is complicated, time-consuming, and is greatly affected by external factors. Relatively speaking, gas chromatography is very simple, easy to learn and understand.
The results of methoxyl content (w1) and hydroxypropoxyl content (w2) in HPMC were determined by gas chromatography and chemical titration respectively. It can be seen that the results of these two methods are very close, indicating that both methods can guarantee the accuracy of the results.
Comparing chemical titration and gas chromatography in terms of time consumption, ease of operation, repeatability and cost, the results show that the biggest advantage of phase chromatography is convenience, quickness and high efficiency. There is no need to prepare a large amount of reagents and solutions, and it only takes more than ten minutes to measure a sample, and the actual time saved will be greater than statistics. In the chemical titration method, the human error in judging the titration end point is large, while the gas chromatography test results are less affected by human factors. Moreover, gas chromatography is a separation technique that separates the reaction products and quantifies them. If it can cooperate with other measuring instruments, such as GC/MS, GC/FTIR, etc., it can be used to identify some complex unknown samples (modified fibers) Plain ether products) are very advantageous, which is unmatched by chemical titration. In addition, the reproducibility of gas chromatography results is better than that of chemical titration.
The disadvantage of gas chromatography is that the cost is high. The cost from the establishment of gas chromatography station to the maintenance of the instrument and the selection of the chromatographic column is higher than that of the chemical titration method. Different instrument configurations and test conditions will also affect the results, such as Detector type, chromatographic column and choice of stationary phase, etc.
2.2 The influence of gas chromatography conditions on the determination results
For gas chromatography experiments, the key is to determine the appropriate chromatographic conditions to obtain more accurate results. In this experiment, hydroxyethylcellulose (HEC) and hydroxypropylmethylcellulose (HPMC) were used as raw materials, and the influence of two factors, column temperature and column length, was studied.
When the degree of separation R ≥ 1.5, it is called complete separation. According to the provisions of “Chinese Pharmacopoeia”, R should be greater than 1.5. Combined with the column temperature at three temperatures, the resolution of each component is greater than 1.5, which meet the basic separation requirements, which are R90°C>R100°C>R110°C. Considering the tailing factor, the tailing factor r>1 is the tailing peak, r<1 is the front peak, and the closer r is to 1, the better the performance of the chromatographic column. For toluene and ethyl iodide, R90°C>R100°C>R110°C; o-xylene is the solvent with the highest boiling point, R90°C<R100°C<R110°C; so for toluene and ethyl iodide with relatively low boiling points, lower the column temperature It can effectively improve the resolution, tailing and peak symmetry, but the lower the column temperature, the more serious the forward-sloping peak of o-xylene. Lowering the column temperature is the easiest way to improve resolution.
The influence of the column length on the experimental results shows that under the same conditions, only the length of the chromatographic column is changed. Compared with the packed column of 3m and 2m, the analysis results and resolution of the 3m column are better, and the longer the column, the better the column efficiency. The higher the value, the more reliable the result.

3. Conclusion
Hydroiodic acid is used to destroy the ether bond of non-ionic cellulose ether to generate small molecule iodide, which is separated by gas chromatography and quantified by internal standard method to obtain the content of the substituent. In addition to hydroxypropyl methylcellulose, cellulose ethers suitable for this method include hydroxyethyl cellulose, hydroxyethyl methyl cellulose, and methyl cellulose, and the sample treatment method is similar.
Compared with the traditional chemical titration method, gas chromatography analysis of substituent content of non-ionic cellulose ether has many advantages. The principle is simple and easy to understand, the operation is convenient, and there is no need to prepare a large amount of medicines and reagents, which greatly saves the analysis time. The results obtained by this method are consistent with those obtained by chemical titration.
When analyzing substituent content by gas chromatography, it is very important to choose appropriate and optimal chromatographic conditions. Generally, reducing the column temperature or increasing the column length can effectively improve the resolution, but care must be taken to prevent components from condensing in the column due to too low column temperature.
At present, most domestic manufacturers are still using chemical titration to determine the content of substituents. However, considering the advantages and disadvantages of various aspects, gas chromatography is a simple and fast testing method worth promoting from the perspective of development trends.