Bad integration: Example [Bioanalytics]
Dear Sagar,
a picture tells more than a thousand words.
Following my previous post – which was a little bit theoretical – let’s look at an example (not from the last century; I received it a couple of days ago):
This chromatogram shows the low CC standard of a chiral separation of drug X; first peak is the (inactive) d-enantiomer and second the (active) l-enantiomer. IMHO the analyst made a couple of mistakes…
a picture tells more than a thousand words.
Following my previous post – which was a little bit theoretical – let’s look at an example (not from the last century; I received it a couple of days ago):
This chromatogram shows the low CC standard of a chiral separation of drug X; first peak is the (inactive) d-enantiomer and second the (active) l-enantiomer. IMHO the analyst made a couple of mistakes…
- He set the integration window in such a way that the first enantiomer was not integrated at all. Debatable from a pharmacokinetic point of view (what if a regulator asks you later on to evaluate the other enantiomer as well?) – but also a killer for the integration algo (see below).
- He relied on automatic integration (black area), which ended too early due to the small shoulder at ≈9 min. If you compare the noise before and after the peaks it’s clear that this shoulder is most likely not an interference, but random noise.
- Even if the second peak would have been correctly integrated by his method (▬▬), the area would be underestimated.
- Only if the first peak is also integrated (▬▬), the peak areas would reflect the enantiomeric ratio of 50:50 of the racemate (which was used in calibration).
- We are currently investigating whether the CRO did not review chromatograms (bad), or had an SOP in place which did not allow manual reintegration (even worse).
—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- Manual integration sagark 2010-07-29 02:26 [Bioanalytics]
- Manual integration Helmut 2010-07-29 15:30
- Manual integration ElMaestro 2010-07-29 21:07
- History Helmut 2010-07-30 01:30
- LSB - evil, terrible and annoying ElMaestro 2010-07-30 23:46
- Manual integration ElMaestro 2010-07-29 21:07
- Bad integration: ExampleHelmut 2010-07-30 20:24
- Bad integration: Example sagark 2010-07-31 12:57
- Bad integration: Example Helmut 2010-08-01 02:09
- Better integration? Example Helmut 2010-08-12 20:11
- Better integration? Example ElMaestro 2010-08-12 23:14
- Better algorithms / more awareness of analysts Helmut 2010-08-13 13:43
- Better integration? Example ElMaestro 2010-08-12 23:14
- Better integration? Example Helmut 2010-08-12 20:11
- Bad integration: Example Helmut 2010-08-01 02:09
- Bad integration: Example sagark 2010-07-31 12:57
- Manual integration keshav khude 2010-08-13 09:11
- Manual integration Helmut 2010-07-29 15:30