Hello Kamleshwar Patle,

It is not possible to determine the yield without calibration.

You can use the following calibration methods:

External calibration/calibration curve

Internal calibration

Standard addition

The simplest calibration is the calibration curve. Measure different concentrations of your analytes and plot the concentration against the peak area. You will obtain a calibration function from the individual data. Ideally, the calibration is linear so that you can calculate the concentration of your sample using the linear equation, but this is also possible with non-linear functions.

However, you should check this function regularly with a control standard to detect changes in the system and adjust your calibration accordingly. In comparison, the internal standard is less complex and only needs to be added to the sample for measurement. Calibration and measurement are performed with the same injection. This method always reflects the state of the system, but is also only a one-point calibration. However, the correction factor between the internal standard and the analyte must be determined in advance. They do not have the exact same response from the detector.

Good luck and best regards

Joachim Horst

3d ago

Kamleshwar Patle

1) How to make standard solution for GC-FID analysis - For Residual solvents calculation, Standard preparation is depend on sample concentration eg. If samples is to be weighed 0.5g ( Crush tablets powder or pure drug substance ) in HS vial. Add appropriate volume like (1 mL,2mL or 5mL). More precisely if you use 5mL volume for dilution then your sample concentration will be 0.5g/5mL = 0.1 time sample dilution(A). This dilution applicable as per ICH limit and further consideration while preparing standard eg. If you would like to quantify Iso-Propyl Alcohol (IPA) Limit as per ICH is 5000ppm so standard will be of 500ppm ( 5000ppm x 0.1 time sample dilution(A) = 500ppm of standard solution.

2) how to calculate the yield by GC-FID without internal standard method? - Without internal standard method is called as external standard method analysis i.e you can use standard of interest and inject replicated to calculate targeted solvents in sample.

Hopefully clarified query. Should you require further clarification feel free to ask

Dear Kamleshwar Patle,

There is only one case where you can go without calibration to quantify when using FID - when all substances in your sample pertain to the same organic classification. The classical example is oil samples that contain only hydrocarbons. Since the FID response will be proportional to the mass and all substances burn with the same mechanism, you can use the peak area percentage of one peak in relation to the total area of all peaks as a content measure without calibration. However, it is a very special case although with strong commercial implications.

If you are analyzing gas samples, it is safe to use sample valves and external standard calibration. However, if you are analyzing liquid samples, I would strongly recommend an internal standard method of analysis as your way.