I have such a problem, and maybe there is somebody here, who could help me with it.
Our laboratory has been developing a method for the medicinal product with lidocaine (96 mg per 1 g of product) that achieves 20% of the acceptable intake (AI) for nitrosolidocaine (100% AI = 0.578 ppm) and 100% of the AI for NDEA (100% AI = 0.153 ppm) so far at best. As these data would cause batch-by-batch testing of the product, we would like to know if any laboratory has experience with this kind of formulation and has developed an analytical method with better LOQ results, so that the testing could be skipped (depending, of course, on the level of nitrosolidocaine and NDEA in the product). The product matrix includes stearic acid, isopropyl myristate, and diethylene glycol monoethyl ether, in addition to lidocaine.
At that level of lidocaine I am hoping this isn’t an orally ingestible product!! Or that the dose is very small.
Can you share your method conditions/column/sample prep/transitions etc.? I may be able to provide some pointers, not from a liquid product perspective, but from something with lower levels of lidocaine. May not work with your formulation with some of your excipients, but could help.
NDEA → APCI works best. We archieved an LOQ of 0.1 ng/mL. GCMS works even better sensitivity wise, but we had problems with coelution in other products. We did not test Lidocain so far for this. Maybe this information will help you.
Nitroso-Lidocain → ESI. We archieved an LOQ of 0.005ng/mL. We measured the M+Na Adduct using 1mM NaOH with 0.1% formic acid. Nitroso-Lidocain M+H, was barely visible.
Depending on our sample concentration in mg/mL this could be enough.
I must say we measured only API so far, so i am not certain how matrix will impact your accuracy.
do you mean concentration of nitrosamines in the mixture with API and excipients I have mentioned at the beginning?
The problems are due the high concentration of API in the measured sample (especially for nitrosolidocaine impurity) as well as with the sample matrix, which is liquid (it cannot be removed it properly from the sample). That is why I am looking somebody with the liquid product with lidocaine.
I mean the concentration of the analyte in solution. You can calculate your LOQ in ppm by dividing the concentration in ng/mL by the sample concentration in solution. This concentration was not mentioned in your post. Or did you inject the liquid formulation directly into your system ?
For example, for lidocaine: 10% AI corresponds to about 0.058 ppm, which in our method would relate to a sample concentration of roughly 0.1 mg/mL. With your formulation, this would mean weighing around 100 mg of product (which corresponds to roughly 10mg Lidocain) into 10 mL of solvent. Most of the time, this level of dilution will be sufficient to eliminate matrix effects, but only testing will confirm this.