I am currently developing an analytical method for the determination of nitrosamines in quetiapine oral suspension using LC-MS/MS. The product contains 20 mg/mL of active substance and the maximum daily dose (MDD) is 800 mg. Accordingly, based on the acceptable intake (AI) limit for the relevant nitrosamine, the calculated specification limit corresponds to 0.13 ppm.
The sample is in suspension form. Following sample preparation, the sample solution is planned to be diluted to an API concentration of approximately 6–8 ppm. Under these conditions, the calculated on-instrument analytical limit for N-Nitrosomethylphenylamine (NMPA) falls below 1 ppb, and the current method does not provide sufficient sensitivity. Therefore, in order to compensate for matrix effects, it is planned to apply the standard addition method by spiking NMPA into the sample solution and calculating the differential response.
What are your opinions on this approach? Would this be a feasible strategy?
If it is a process impurity, why don’t you just do the testing at API level? unless you have confirmation of carry-over of the precursor amine, it should not be forming in DP, so you can establish control at that level. NMP carry-over should not be of concern.
I agree with Javier and that’s why I asked in the first place.
considering that NMPA is an API process related imp, you could demonstrate absence studies in API level, and perhaps any theoretical assessment, purge analysis justification for FP.