Chromatography Forum

Hi guys,

I am trying to do a sample prep.
The limit of the impurity (phatalate) is 5 µg per gram API.
I want to analyze it on GC-MS in SIM.

It is actually a mass/mass determination and it is not possible for me to weigh in 500 µg of phtalate because I don't have 100 gram of API.

The solvent I will use is ACN.

What is the best way to determine the 5 ppm in gram API?

I was thinking, if 5 ppm is in 1 gram of API and I dissolve 1 gram API in 100mL, isn't it is the same as 5 mg /1000 mL = 0.5 mg /100 mL = 0.5 mg /g of API = ug /g of API?

So if I dissolve 0.5mg of phtalate in 100mL ACN, than I can analyze 5 ppm in 1 gram API right?

Sorry if my English is not correct, i am from the Netherlands.

Thank you all in advance

5 ppm is HUGE! As per ICH Q3 on related substances the limit is 0.05% relative to the API dosage. If the drug substance dosage is 10 mg (example tablet) then your LOQ should be 0.005 mg or 5 ug (not counting dilutions). Typically I would achieve an LOQ of 50 ng/mL on a DAD.

I would use chromatography (either HPLC or GC) as the preferred analytical procedure.

5 ppm is HUGE! As per ICH Q3 on related substances the limit is 0.05% relative to the API dosage. If the drug substance dosage is 10 mg (example tablet) then your LOQ should be 0.005 mg or 5 ug (not counting dilutions). Typically I would achieve an LOQ of 50 ng/mL on a DAD.

5 ppm = 0.0005%
Not so huge

5 ppm is HUGE! As per ICH Q3 on related substances the limit is 0.05% relative to the API dosage. If the drug substance dosage is 10 mg (example tablet) then your LOQ should be 0.005 mg or 5 ug (not counting dilutions). Typically I would achieve an LOQ of 50 ng/mL on a DAD.

I would use chromatography (either HPLC or GC) as the preferred analytical procedure.

If you take a sample that is 1g, then what ever ppm or % you determine will scale back to a 10mg dosage. If 1g contains 4ppm or 0.0004% then 10mg will contain 0.0004% or 0.00004mg or 0.04ug of phthalate in a dose of the API.

So in sample prep you need to find 5ug/g so if you detect 5ug/100ml or 50ug/L then you can prep your sample and standards by extracting 1g sample with 100ml solvent. You can make a higher concentration of phthalate in acetonitrile and inject a few ul into the 100ml acetonitrile to give the 5ppm concentration. Example is you make a solution of phthalate in acetonitrile at 5000ppm then you spike 100ul of that into the 100ml extract to have 5ppm in the extract, if you make the standard 50000ppm then you only need to inject 10ul into the 100ml of extract for 5ppm.

Superb!

Thank you for the example you have given me James.

Now I know how to determine 5ug phtalate in 1 gram API