Chromatography Forum

how long does one chemist take to develop a LC method for QC dept?

Anywhere from a day to several months. Depends on how "difficult" the analysis (how many analytes, how complex the matrix, what linear range and/or detection limits, how "well behaved" the analytes, . . . etc.).

I just developed a gradient HPLC for two preservatives of differing polarities, got decent results the first morning. A week later, moved the technology to a more-appropriate column, took another few hours.

Much better chroamtography than the supplier's procedure, as we found out a few weeks after that.

But some analytes or matrices can be tricky, maybe up to a month. Like we did isocratic sunscreen lotion with 5 peaks, less than 8 minute isocratic run, all peaks with better than resolution of 2.0 (pharmaceutical product), seem to remember that took about a week.

How long is a piece of string ?

For HPLC of three compounds in a crude natural product extract (two of them minor components) took me 9 months (admittedly not all of it full time) and about 1500 runs to tweak mobile phase, gradient and sample prep (it had to work with mg quantities of crude extracts). No wonder I prefer GC !

Peter

Just to compare and contrast here...

Both API impurity methods.

The first method was for a proprietary compound with about a 15 step synthesis. So, I was looking for roughly 15 impurities. This took about two weeks to develop and about another two weeks to complete the validation work in an FDA regulated environment. This was a %area method and impurity spikes/linearity/recovery/stability/relative response factors were not required to be evaluated.

The second method is an impurities method for a halobetasol product. Five impurities from synthesis, one known degradation impurity. Development time took 6 months. Validation took about a month and a half. This was a % wt/wt method and impurity spikes/linearity/recovery/stability/relative response factors were evaluated.

The difference? That second method has massive LOD/LOQ problems, which required continual optimization of the sample solvent and gradient. The product also had solubility problems, which made sample solvent optimization challenging at best. In addition to that, the one known impurity is nearly identical to the API itself in structure. Obtaining a resolution of 2.0 or greater between the API and impurity was nearly impossible. Changing the sample solvent and/or gradient wrecked resolution every time. If the peaks became too broad, I would not meet LOD/LOQ requirements ... and the vicious circle begins.

The point of this post being, to reinforce what others have already said, this is not a cookie cutter process and there is no scaling (ie it takes one week to develop a method for 1 compound, so it will take a month for 4) as shown by my 15 compound impurity method being developed in 1/12 the time of a 6 compound method.

Keep in mind also that what is considered to be a "method" can vary from lab to lab. Some might consider an LC method to be any combination of column and conditions that produces a reasonable looking peak from a single component standard, others might want the full house validation.

Peter

approximately 3 hours per peak of interest, quantity divided by the initial injection's resolution for the critical peak pair, square that result if it needs to be stability indicating (because you need forced degradation, known impurities etc.), times 4 if it needs to be fully validated.
(can you tell it's Friday?)