USP Methimazole - Poor detection with Agilent 7890

[Philip01]

Hi all,

We've been working on the USP Monograph for "Methimazole" but we're having trouble with the Organic Impurities method. (The method is the same as mentioned in the EP monograph for "Thiamazole".

Problem:
The problem we're experiencing is the detection of the impurities, USP Methimazole Related Compound A, 1-Methylimidazole and USP Methimazole Related Compound C. The concentration of these are 0.01mg/ml in chloroform.

Method Conditions:

Inlet Temp 150°C
Detector 250°C
Flow Rate 1.5ml
Injection volume 1μl
Carrier Gas Helium
Split Ratio 3:20
Oven: 100°C for 2mins.
30°C/min ramp to 250°C with a hold time of 15mins at 250°C

Column: 30m x 0.25mm; 0.5μm (G27)

The column we are using is an Agilent DB-5 column with a split ratio of 1:10 to prevent a long solvent front with our diluent, Chloroform. The liner we're using is an Agilent single taper, glass wool with an ID of 4mm.

Troubleshooting Steps we've performed:
We have performed a series of spike injections with a more concentrated solution to establish were the retention time of our peaks came out. For reference Methimazole is ~6.5mins, with Related Compound A having a RRT of 0.3, 1-Methylimidazole a RRT of 0.4 and Related Compound C a RRT of 0.7. Rather than using a 0.01mg/ml solution we performed an injection with a concentration of 0.2mg/ml which gave us peak areas of ~40 to ~50. We have replaced our glass liner, septa and O-Ring as well as reducing the split ratio to 1:5 and increasing the injection volume to 2μl but to no avail.

Any advice would be greatly appreciated, thanks.

[Consumer Products Guy]

Hi all,

We've been working on the USP Monograph ...

Any advice would be greatly appreciated, thanks.

I found that such USP methods frequently had issues. Sorry.