We are developing a new method for the quantitation of the degradation products in the bulk drug and bulk product.
Our acceptance criteria for the LOQ value is to be less or equal to the 50% of the 1% of the assay sample concentration (for example: if the assay sample concentration is 4 µg/mL, the LoQ must be equal or less than 0.02 µg/mL)
We were requested by the Quality Control Laboratory to develope a method with an LoQ less or equal to the 0.1% of the assay sample concentration. The rationale for this petition is based on the requirement to characterize and identify any unknown peak with an area higher than 0.1%. Therefore, the method needs to be capable to detect that 0.1% concentration.
Question:
Do all the methods need to have LoQ values at least equal to the 0.1% of the sample concentration?

No, LOQ is usually quoted as 10 times s/n, and LOD is either 2 times or 3 times signal to noise ratio (s/n). This can be derived from stats considerations if you don't feel that its easy measuring the noise levels.
It is something which is dictated by your method/equipment, not someone in your QC/QA department.
You tell them what your LOD/LOQ is from experiment, they tell you if its good enough.
Cheers
Bryan Wallwork
Bryan Wallwork

Hi Sara,

All methods do not need to be developed/validated with a LOQ of 0.1%, however, stability indicating methods do.

I recommend that you follow the link below and review the guidance documentation on validating analytical methods, stability indicating methods, etc.

http://www.fda.gov/cder/guidance/index.htm

I disagree with Brian above. Assume that your detector has a noise level of 0.02mAU. Thus, the LOQ signal level is approximately 0.2 mAU (10xnoise). However, what this absolute signal level maps to in relative concentration is completely dependent on your method (assuming you have control of sample preparation, injection volume, etc.). For example, if you adjust your sample prep/injection volume to produce a 200mAU peak at the 100% level then an injection at the 0.1% would be approximately 0.2mAU and would be approximately LOQ. Now, if instead you target the 100% level at 800mAU LOQ would be 0.025%

Within limits, you are in direct control of the LOQ. Good Luck.

Well, it seems that LOQ is what ever you want it to be (smacks of Alice in Wonderland and Lewis Carroll!!)
The LOD/Q is determined by four things,
a)the noise level of the system you are using
b)the molar extinction coefficient of the compound of interest at the wavelength/pH chosen
c)dilution effect of the instrument you are using
d)the mass of compound of interest injected

Generally (this is where you may disagree!) a,b & c are fixed in a method, so the LOD/Q is dependant on the mass injected. If the concentration of your sample is also fixed (as in your example 4µg/ml), then all you have to play with is the sample volume, and with typical analytical columns, this means 20µl or less, to maintain column efficiency. So LOD/Q is not what ever you want it to be after all, it can only be equal or greater to it, but never less than that dictated by the above.

..and Tom, not everyone works to FDA regulations, there if life outside of the US!!

Bryan,

The link I posted is to the US FDA web site but it contains both the final and draft ICH documents which some may find helpful, even some outside of the US.

Regarding LOQ, you are correct in an absolute sense (mass on column). However, most HPLC quantitation is performed in a relative sense, based on either an external or internal standard. Thus, you are, or at least should be, in control of the function that maps mass on column to percent of drug. Good luck, I've got to go find my rabbit hole.

Cheers,

Tom