Ph. Eur. method 2.4.24 Residual solvents

[dezelana]

Dear colleagues!
I am asking again for advices since I haven't got any response. I do not fully understand Ph. Eur. method for the residual solvents determination-how to prepare residual solvent solutions. Does anybody deal with this method?
Now also American pharmacopoeia USP use similar method-No 467.
Please help

anand

[Brefie]

in water soluble:
Solvent in 20ml DMSO (for example 76µlmethanol)
Dilute 5ml in 100ml H2O (ref)
In Vial: (ref sol b):1ml ref +5ml h2o
test sol 5ml sample sol +1 ml blank

ginou

[dezelana]

Hello Ginou!
I was very glad when I saw a reply, although it was so short I do not understand it. I suppose my question was not enough precisely.
So, For example-the specification for te residual solvents methanol and chloroform in some substance is:
methanol: not more than 3000 ppm
chloroform: not more than 60 ppm
I do not know how how to prepare Solvent solution (b) and Solvent solution (c)-how much solvents should I weigh in what volume?
I do not understand why this two solutions should have a concentration of the solvents 1/20 of the limits stated in Table 2.
At the same time-do you meet the requirement for the resolution between acetonitrile and methylene chloride peak by using required chromatographic system and which column do you use. We tried AT 624 mega bore and 0,32mcm but peaks coelute.

I would appreciate your answer
ana

[Brefie]

Hy Ana,
My reply was so short because I don't write good english.
So I try. For solvent solution b: 76µl Methanol 10µ ACN and 9µDichlormethan in 20 ml DMSO than dilute 5ml to 100ml with H2O. We have 15mg/ml Methanol (3000/20=150).
For solvent sol. c weight 1g in DMSO an dilute more time with water to have a conc of 15mg/ml Methanol.
So and why is the conc 1/20e ? I don't know but I thing anyway that the RS methode is to complicate and we have the first time we had do it, ask many questions.
I meet the requirement with a DB-624 30m*0.32mm 1.8µm ID, 50 Kpa He, split +5ml/min
Ginou

[Brefie]

Ana,
The conc. must to be 1/20 because in your vial you have 1/20 of 1g (50mg) :

Ginou

[dezelana]

Hello Ginou!
Thank you very much for your quick reply. I calculated now and I think it will go now. But in solvent solution (b) the methanol concentration is 0,15 mg/ml and not 15mg/ml (76mclx0,79=60mg 60x5/20/100=0,15). Am I correct or Idon't understand well?
Than in Reference solution (b) it is:0,15/6=0,025mg/ml; 0,025x100/8,333=3000 ppm-this is OK for methanol

I have to try now (I hope soon) and if something will be wrong I will write again. Thank you again
Ana