What should I do if my chromatogram encounters a leading edge peak?
✔ 01The influence of frontier peak1️⃣ A. Calculation of impact peak height
When the peak areas are the same, their peak heights will differ greatly due to the peak front. This has an impact when we use peak height to calculate sample results, especially when calculating the minimum detection limit.
2️⃣ B. Calculation of peak area affected by
When calculating peak areas, the start and end points of the peak are generally determined by the slope of the chromatographic peak. At the front of the chromatographic peak, the flatter the front baseline, the more difficult it is to confirm the starting point, resulting in inaccurate peak area quantification.
3️⃣ C. Affects the confirmation of certain trace components
When the resolution of the previous peaks is not very good, the sample peaks will be easily hidden at the leading edge of the later peaks and cannot be calculated.
✔ 02. Cause analysis and solutions for frontier peaks
1️⃣ A. Column overload
Each chromatographic column has its maximum sample carrying capacity. When the sample amount is too large, overloading will occur, including mass overload and volume overload. We can see whether the peak shape is improved by reducing the sample amount or sample concentration. It can also be solved by increasing the column diameter and using a higher capacity stationary phase.
2️⃣ B. Improper selection of sample solvent
The leading edge peak occurs when the elution power of the sample solvent is much stronger than that of the mobile phase. Specifically, if the sample moves forward uniformly in the chromatographic column, we will usually get a normal distribution of peaks. When the sample solution reaches the chromatographic column in a relatively short time after injection and is not fully diluted by the mobile phase, due to the presence of a sample solvent with relatively strong elution ability, some samples are eluted faster and pass through the chromatographic column quickly, and finally Leading to peak front extension.
3️⃣ C. Chromatographic column damage
After long-term use of a chromatographic column, the silica gel packing will dissolve and the column bed will collapse, resulting in reduced column efficiency and leading to peak fronting. If it is found that the column is damaged, it is recommended to replace the column directly.
4️⃣ D. Peak interference
The two compounds co-elute, that is, a small peak appears before the large peak, and the chromatographic peaks are not separated. Interference can be reduced by adding sample purification procedures. The mobile phase can also be adjusted to improve resolution.

Dissolution is an area where I've found that training tends to be lacking. In many companies, dissolution is taught to a chemist from another chemist - and the fundamentals of dissolution can be missed. Luckily, there are several resources to learn the basics of dissolution and help you to understand not only what you're doing in dissolution - but why and how you are doing it the way that you are.
Depending on how you prefer to learn, here are some good ways to elevate your knowledge.
First, I recommend starting with USP <711> Dissolution. This isn't a long chapter, and I think it is important to start with a strong foundation.
Next, there are some different free resources available to help you learn as well. If you prefer learning by webinars, there are many dissolution webinars available at: https://lnkd.in/gw9qrUD
Many of those webinars are ones I've put together and have information I feel is meaningful and relevant for the topics. If you're just starting out, go to the Dissolution: Foundation to Innovation Series and begin with Fundamentals.
If you'd like a more interactive training, Agilent has a free fundamentals training at: https://lnkd.in/eMhmJM8w
Much of that material was put together by Bryan Crist, who has been a mentor to me for many years.
Want to see what's going on with dissolution? LinkedIn can be helpful there, and there are dissolution and pharma focused groups to stay up to date. Dissolution Technologies magazine is great to check out as well at: https://lnkd.in/g_NeYhrK
Hopefully, you find I'm a helpful resource to you as well.