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chandru
Junior

India,
2018-02-14 07:31
(edited by chandru on 2018-02-14 10:02)

Posting: # 18416
Views: 1,991
 

 Concomitant medications experiment in method validation [Bioanalytics]

Hi all,

How to evaluate the effect of concomitant medications during validation?

We add the concomitant medications to LLOQ of analyte and compare against the calibration standard.

Any additional experiment has to be performed to evaluate its effect.

Regards,
Chandru
Obinoscopy
Regular

Nigeria,
2018-05-02 04:05

@ chandru
Posting: # 18745
Views: 1,192
 

 Concomitant medications experiment in method validation

Dear Chandru

» We add the concomitant medications to LLOQ of analyte and compare against the calibration standard.

For concomitant medications, you compare the LLOQ (spiked with concomitant medications) with Blank Samples (also spiked with concomitant medications) and calculate the signal to noise ratio (or %interference). Response of interfering peaks at the retention time of the analyte for the blank samples should be less than 20% of the lower limit of quantification for the analyte and 5% for the internal standard.

» Any additional experiment has to be performed to evaluate its effect.

Precision and Accuracy needs to be evaluated for the range of CC standards (spiked with the concomitant medications)

Incurred Sample Reanalysis also give an insight on the effect of concomitant medications.

These are my thoughts.

Regards,

Scopy
ElMaestro
Hero

Denmark,
2018-05-02 09:25

@ chandru
Posting: # 18746
Views: 1,170
 

 Concomitant medications experiment in method validation

Hi chandru,

» How to evaluate the effect of concomitant medications during validation?

Wow, that is actually a great question, and a controversial one.

Some CROs believe that when they do LC-MS/MS they don't have to evaluate it. Interference is impossible, there would never be an interfering transition, testing for it is a waste of time, inteference like ion enhancement has never been seen, and some singing and dancing to that tune.

The better CROs, and here better is in this regard a purely subjective term reflecting just my personal opinion, will test A+P by spiking the QCs at roughly Cmax levels they get from the literature (incl. prescribing info, SPCs, PARs) along with a check of interference on blanks. Some will do the spiking experiment individually, and some will do it with a cocktail. Both approaches seem to be widely accepted by agencies.
It is furthermore becoming a proper practice to have an SOP in place so that the lab is informed of any concomitant meds that are given, and if a drug has been given which wasn't part of the validation, then there will be an adhoc interference experiment for that drug (non-cocktail type).

if (3) 4

Best regards,
ElMaestro

"(...) targeted cancer therapies will benefit fewer than 2 percent of the cancer patients they’re aimed at. That reality is often lost on consumers, who are being fed a steady diet of winning anecdotes about miracle cures." New York Times (ed.), June 9, 2018.
Ohlbe
Hero

France,
2018-05-02 11:36

@ ElMaestro
Posting: # 18747
Views: 1,158
 

 Enhancement from concomitant medications

Dear ElMaestro,

» interference like ion enhancement has never been seen

It has. There may be some more recent publication, but I have this one in my archives:

Rachael Leverence, Michael J. Avery, Olga Kavetskaia, Honggang Bi, Cornelis E. C. A. Hop and Arkady I. Gusev
Signal suppression/enhancement in HPLC-ESI-MS/MS from concomitant medications
Biomed. Chromatogr. 21: 1143–1150 (2007)
doi:10.1002/bmc.863

Regards
Ohlbe
ElMaestro
Hero

Denmark,
2018-05-02 12:23

@ Ohlbe
Posting: # 18748
Views: 1,155
 

 Enhancement from concomitant medications

Hi Ohlbe,

» It has. There may be some more recent publication, but I have this one in my archives:

I feel I am not the right target audience. :-D

if (3) 4

Best regards,
ElMaestro

"(...) targeted cancer therapies will benefit fewer than 2 percent of the cancer patients they’re aimed at. That reality is often lost on consumers, who are being fed a steady diet of winning anecdotes about miracle cures." New York Times (ed.), June 9, 2018.
Ohlbe
Hero

France,
2018-05-02 12:34

@ ElMaestro
Posting: # 18749
Views: 1,142
 

 Enhancement from concomitant medications

Hi ElMaestro,

» I feel I am not the right target audience. :-D

Hopefully there are some people in the right target audience who monitor this forum, or to whom this reference will be re-directed :-)

Regards
Ohlbe
chandru
Junior

India,
2018-05-27 21:41

@ Ohlbe
Posting: # 18820
Views: 868
 

 US FDA guidance

Hi thank you all for your valuable inputs.

After the release of FDA guidance May 2018, is it mandatory to evaluate stability of molecule in presence of potentially interfering substance?

Is it mandatory to evaluate for all the concomitant medication given to subjects in a particular study or is it ok if we do it for regularly administered drug(eg., Some defined 10 drugs, putting in the SOP and evaluating it) ?

Regards,
Chandru
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