Learnaboutgmp Community

Determination residue for cleaning validation

Hi there,
i want to ask about cleaning validation. im doing cleaning validation of Mefenamic acid tablet. and i’m using rinse method using solution NaOH 0,1 N (Sodium Hydroxyde). and i want to ask after i take the sample (using rinse method) i have to determine the residue of NaOH right? and i found very difficult to determine cause the concentration the solution is very small ( i think in ppm). so what method should i take to determine the residue of NaOH solution?
thank you:confused:

dear mam

you can do the alkalinity test to determine the presence of NaoH. through this method u can identify the presence of NaoH

gagandeep

dear gagandep,
i use the lakmus paper and the result is netral. what other method should i take to determine the NaOH solutions?
and i want to know, what do you think about after taking sample (using rinse method) with NaOH solution to a super mixer, i rinse the super mixer third time with water. do you think the NaOH solution will dissapear?
thank you, waiting for the reply
:slight_smile:

Dear rika_ndry,

litmus paper has a quite low sensitivity. To detect traces of NaOH I would try conductimetry.

If I understood your procedure well, your contaminant is mefenamic acid, you clean it with sodium hydroxyde and to validate the cleaning process you measure completion of rinsing detecting absence of sodium hydroxide. As an advice, by this way you have not demonstrated that you completely removed the mefenamic acid, but only the cleaning agent (NaOH) at best. Although it is logical to think the mefenamic acid has been removed being solubilized by the NaOH, it is an assumption that has to be demonstrated. If you prove that the method is succesful and validate it, the traces of NaOH can be used as a marker for routine monitoring, but not for validation.

Best regards

Alfred

I completely agree with Mr. Alfred

dear alfred,
this is the procedure that im doing :

  1. i clean the equipment using only aqua DM (according to the SOP).
  2. after cleaning, i take the rinse sample with NaOH solution (because mefenamic acid soluble in NaOH sol).
  3. after taken the sample, i rinse the equipment with Aqua DM (3x).
    then im take the measurement.
    what do you think?
    and how detecting the NaOH using conductivity meter?
    thx

Dear rika_ndry,

as i told you in my former post, by this way you demonstrate, at best, that you have eliminated the sampling solvent (NaOH solution) from the equipment, but not your target substance, the mefenamic acid. Although mefenamic acid should be soluble in NAOH solution, it is not proven that rinsing with NaOH actually withdraws all the mefenamic acid (if you could prove that, you could use your sampling method as cleaning procedure!). The best approach would be to carry out a recovery test, spiking a surface that is representative for the equipment’s surface with a known amount of mefenamic acid, (ideally near the expected and/or accepted target level of mefenamic acid), rinsing that surface with NaOH solution proportional to the rinsing volume of the equipment, and analytically measuring the traces of mefenamic acid (or its sodium salt) in the NaOH solution. The ratio of spiked amount/measured amount of mefenamic acid will give you the recovery factor (not recovery rate!) with which you will have to multiply later the amount of mefenamic acid encountered in the equipment. If this factor is acceptable (usually less than 2, that means you have recovered more than 50% of the initially spiked mefenamic acid), the next step is to sample the equipment with a fixed quantity of NaOH solution, measuring the traces of mefenamic acid, multiplying the result with the recovery factor and thus getting the real quantity of mefenamic acid left in the equipment after cleaning it. The point is that to measure contamination with mefenamic acid you need to look for mefenamic acid, and thus need an analytical method for mefenamic acid. Every other approach has to rely on a previous demonstration that your measurement can be correlated to a mefenamic acid level. The measurement of NaOH by conductivity (or alternatively with a pH-meter) is very easy because it boils down to place the rinse solution in the equipment cell, but as you use it as sampling solvent it does not give you any clue of how many mefenamic acid is or was there in the equipment.

Best regards

Alfred

Hi all,
I have seen a very nice discussion between you guys. I want to ask what is the amount of NaOH you have taken during the sampling of mefenamic acid? if the method is not determining the NaOH then you should make an attempt to reduce the amount of NaOH and determine the new recovery.
Furthermore, you should also try coupon sampling to improve your sampling method. May be you need to improve your sampling methods and analytical methods.

Tell me what is the acceptance criteria that you have set for the residue of the NaOH?

Prawan Dahal