Fang Hanmin believes that medicine is a special product for treating diseases and saving people, and there is no room for negligence, even if it costs a lot, it is necessary to understand the various ingredients in it.

First of all, once the composition of this impurity is known, it can be judged how it is generated during the synthesis reaction, and by changing the process conditions, the formation of this impurity can be minimized or eliminated, which is conducive to further improving the product quality.

In addition, after the successful development of the drug, it needs to be registered with the regulatory authority, and the analysis and test results of the drug must be presented to the regulatory agency at that time, because when it comes to the evaluation of toxic and side effects, each of the ingredients, including impurities, must be clearly identified, otherwise, the regulatory authority will not give registration approval.

Fang Hanmin explained the reason to the colleagues in the generic drug research group and the analysis and testing institutions, and he asked Wang Gong to contact the relevant domestic institutions as soon as possible to make a qualitative analysis of the impurities in the samples as soon as possible.

After consulting with his university teacher, Wang quickly contacted a top scientific research institution, and after explaining his intentions on the phone, the other party said that he could do qualitative analysis of their samples, but the fee was relatively high. In addition, the content of the substance required to be qualitatively tested must not be less than 50% in the sample.

Fang Hanmin doesn't care about the fee, but the content of unknown substances in the sample is only 1%, which is too far from the requirements of the testing agency!

"Under normal circumstances, the entrusting party only provides the samples to be tested, and the rest is the business of the entrusted party, how can they make such a request?" The traverser had experienced similar incidents in his scientific research work in his previous life, and he was no stranger to the relevant procedures, which Fang Hanmin did not understand.

"My university teacher and this scientific research institution to deal with more, according to his analysis, this kind of instrument in the country only five or six, in recent years, the domestic scientific research work is unprecedentedly active, need to do qualitative analysis of the business queue up, the staff of the entrusted agency in order to reduce the workload, let the client to the sample needs to be qualitative components concentrated to more than 50%, so that they can improve the detection efficiency."

"No, trace components can also be qualitatively analyzed!"

"Yes, trace components can also be qualitatively analyzed, but the qualitative detection process is more cumbersome, because the main components in the sample interfere greatly with the test results, and in order to get the correct conclusion, it is often necessary to test multiple times and compare the test results repeatedly."

Fang Hanmin nodded in agreement, "Allowing the client to concentrate the tested components in the sample to more than 50% can greatly reduce the interference, without the need for multiple tests, thus saving a lot of time for analysis and comparison, and indeed reducing the workload, which is a good idea." ”

"The problem is to concentrate the unknown content of the sample from 1% to more than 50%, which is not a small task!" Guo Peng stood aside and shook his head.

After a short silence, Fang Hanmin said helplessly: "The difficulty is not small, but if people have such requirements, we have to do what they ask." ”

Of course, Fang Hanmin knows the difficulty of this work, to concentrate the unknown content in the sample to more than 50%, only the recrystallization method and the multiple extraction method, the principle of the two methods is basically the same, but it is not easy to find a suitable solvent.

After analyzing the characteristics of the two methods, Fang Hanmin believes that the operation process of the recrystallization method is too cumbersome, and many tests need to be done to find the right solvent, although the screening of the extraction solvent is still a difficult task, but the extraction method is relatively simple and easy.

Theoretically, as long as the right solvent is found, all that remains is to repeat the extraction operation and concentrate the extract. However, because the physical and chemical properties of unknown substances are not known, they can only be screened through trial and error, which is a troublesome and time-consuming task.

After putting forward some guiding opinions and suggestions on the specific operation, Fang Hanmin asked the analysis and testing agency to cooperate closely with the research team and seize the time to carry out the test. ......

Leaving the laboratory, Fang Hanmin saw Lao Hou, the head of the personnel department, walking towards him in the corridor, Lao Hou was the first middle-level leader Fang Hanmin knew, and there was a special relationship between the two, in the process of Fang Hanmin entering the factory as a temporary worker and later becoming a regular, Lao Hou helped him, although Fang Hanmin has now become the leader of the Red Star Pharmaceutical Factory, but every time they meet, he respects Lao Hou very much.

"Section Chief Hou, where are you going?" Fang Hanmin took the initiative to greet warmly.

"Director Fang, I went to your office just now, I saw that you were not there, it is estimated that you are in the technology center, do you have time now? I'm here to report back to you. ”

"Oh, let's come in and talk." Fang Hanmin also has an office in the technology center, and he let Lao Hou into the room.

Closing the door, Section Chief Hou briefly reported to Fang Hanmin the statistical verification results of the "young and promising" scientific and technological personnel, and handed the bound several pages of the table to Fang Hanmin, "Here is a brief introduction of the relevant personnel. ”

Fang Hanmin took a cursory look at it and felt quite satisfied, "The task assigned last week was completed so quickly, you guys are very efficient!" ”

"The Red Star Pharmaceutical Factory has not officially allocated housing for more than 20 years, and the staff of Corey are all vigorous and eager to do things related to housing allocation, and everyone hopes to finalize the plan as soon as possible."

Is this true? Have you checked it carefully? Don't let those opportunists take advantage of the loopholes! In this matter, Fang Hanmin was very cautious.

In order to dispel Fang Hanmin's doubts, Section Chief Hou gave a detailed introduction to the implementation process of this work. After receiving the task, Lao Hou discussed the investigation plan with Wan Cheng, the head of the technical section, Wan Cheng was young and did not have much administrative work experience, so he could not propose a feasible method, but he was willing to listen to Lao Hou's opinions with an open mind.

Section Chief Hou believes that this work is best carried out separately, first by the technical section according to the spirit of the factory's instructions, to the grass-roots team issued a questionnaire, in the questionnaire to indicate the "young and promising" conditions, workers can be compared with their own situation, as long as they feel that they meet the conditions, you can declare the "young and promising" talents of the Red Star Pharmaceutical Factory, but in the declaration form need to detail their contributions, and have the grassroots leaders and at least one colleague to sign and testify.

The Technical Section is only responsible for issuing questionnaires and collecting declarations, which are then forwarded to the Personnel Section for verification.

On the basis of the declarations received, the staff of the Personnel Section identified the parties and witnesses, verified them one by one, and if the situation was true, confirmed that the parties were "young and promising".

"Well, that's a good idea! However, in the process of verification, have you found any people who are cheating and opportunistic? Fang Hanmin is very satisfied with the work of the two departments.

"There are not only them, but there are several, all of them are production teams at the grassroots level. For example, there is an employee named Lai Qingyuan in the second workshop, he also filled in the declaration form, we verified it according to the content he filled in the form, and found that the signatures of the grassroots leaders and witnesses were fake, because the leaders of the second workshop did not sign him at all, and the witness he filled in, the second workshop found no such person! ”

"Hahaha!" As soon as Section Chief Hou's words fell, Fang Hanmin burst out laughing, "When you mentioned the name Lai Qingyuan, I thought that something would definitely happen, because I know this person too well!" However, although the signatures and witnesses of the grassroots leaders are fake, are the contributions he said really true? Although I have a bad impression of him, I can't bury his contributions. ”

Lao Hou waved his hand, "What a contribution!" What he said was completely false, and the two leaders of the second workshop and his team leader had never heard of it! ”

"See? Your trick is very effective, and it completely eliminates those speculators who deceive. Nevertheless, in order to make this matter more fair and transparent, I suggest that this list be publicized throughout the factory, and if there is no objection within a week, it will be approved. ”

Lao Hou felt that the verification of the personnel department had been done seriously enough, but he didn't expect Fang Hanmin's requirements to be stricter, "Okay, I'll print and distribute this list to each grassroots team to see if there are any different opinions." ”

......

Although the generic drug research team has carried out the test, there has been no progress in several tests, and the scientific and technological personnel of the research group are helpless, and Fang Hanmin also feels incredible, "None of the five extractants that have been used have any effect?" ”

The twists and turns of the test process made Guo Peng and other scientific and technological personnel depressed, "I have used several extractants, and the results are almost the same, what else can I do next?" ”

Fang Hanmin looked at the test record, thought for a while, and then said: "The effect of alcohol solvents is not good, you can try ethers, lipids and nitrogen-containing solvents, because what you want to extract is an unknown substance, and you can only find a suitable extractant through multiple tests, so you must be patient and don't be discouraged." ”

Following Fang Hanmin's train of thought, the research team conducted more than 20 tests, and finally found a lipid solvent with a very good extraction effect on unknown substances.

This result was very encouraging to the research team, and they quickly used this extractant to concentrate the unknown content of the sample to more than 50%.

The staff sent the samples that met the requirements to the authoritative appraisal agency, and a week later, the qualitative analysis results came, and it turned out that this unknown substance was an aromatic nitrogen-containing organic substance, judging from the molecular structure, the substance was indeed formed during the synthesis reaction.

After inquiring about the toxicity data, Fang Hanmin was taken aback, "Fortunately, it was found in time that if the original drug samples obtained so far are declared to the regulatory authorities for the record, once approved and put on the market, the toxicity of this substance will cause great harm to patients taking the drug!" ”

Knowing the molecular structure of this impurity, we can make a judgment on its source, Fang Hanmin and Guo Peng and other scientific and technological personnel to find the cause from the reaction mechanism, improve the synthesis process, and minimize the amount of its generation, while looking for a way to eliminate impurities to minimize its content in the original drug.

After several explorations, it was finally found that the ratio of raw materials and the synthesis reaction time are the two key factors affecting the formation of impurities. In the subsequent test, the optimal material ratio was first determined, under this condition, as long as the synthesis reaction time was controlled within six hours, the formation of toxic impurities could not be detected, and once it exceeded six hours, this impurity gradually increased.

"It's simple, control the synthesis reaction time within six hours, and the toxic impurities will be completely eliminated." Guo Peng looked very happy.

Fang Hanmin reminded: "You ignore the fact that when the synthesis reaction time is not more than six hours, the conversion rate of the main raw materials is only about 45%, and even less than 50%, which will bring great trouble to the subsequent separation and purification!" ”

"Although the conversion rate of raw materials is relatively low, the raw materials that have not been converted can be recycled without causing waste, and I think as long as the generation of toxic impurities can be eliminated, the process is reasonable."

Fang Hanmin disagrees with this view, "You have to remember that what we are doing is applied research, which is different from the purpose of basic research. ”