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The following message was posted to: PharmPK
Dear All,
For one study we need around 1000mL of Rat Plasma and as we all know
it is very difficult to get this much quantity of blank plasma.
So can I perform one cross validation by preparing CC's in Human
plasma and all the QC's in rat plasma and if the experiment is meeting
acceptance then same can be use for the analysis of study sample.
Is this is valid by Regulatory authorities.
If anyone can provide me some proper link for the same.
Regards
Vishal shah
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Dear Vishal,
I believe you require rat plasma for execution of Toxicokinetics or Pharmacokinetics study. With the availability of sensitive instruments (LC/MS/MS) and kind of doses used in these studies, approx. 100uL of plasma per time point required for analysis. With this processing volume, approx. 100mL plasma is required for full method validation and study sample analysis.
Regarding usage of human plasma, there is no provision in guidelines but many people shared their views on this and implemented in routine PK. But how far this is valid for regulatory submission is a question !
regards,
Jignesh
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It's expensive but not difficult to obtain. If expense is the concern why not apply the same logic and use PBS with added albumin or PBS alone? The answer is that rat plasma differs from human (enzyme profile, etc.). A rat's sex hormone binding protein cycles at a much greater rate than does that molecule in human. You would also need to show stability (bench top, extract, freeze thaw and interference (specificity). The questions will be there for anything you did not address in validation. You propose only looking at a small part of a validation exercise and then assume that everything else will fall in. In the end it is essentially a full validation.
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The following message was posted to: PharmPK
Hi Vishal
How much is your per sample processing volume requirement? If you could get
away with lower volumes which of course is determined by the sensitivity of
the assay, you may be able to reduce your total rat plasma requirements.
Manish
Manish Issar, Ph.D
Project Manager
Applied Biopharmaceutics, LLC
2010 Cascade Drive
Corona, CA 92879
Email: m.issar.-at-.gmail.com
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I would be afraid, since the rat's esterase activity is higher than humans.
Stanley Cotler
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The following message was posted to: PharmPK
Actually drug which we are going to analyse is in free
form, encapsulated form and total drug from the plasma which requires 3
different method of analysis, that why we require more Rat plasma
volume.
That why we are thinking of cross validation.
So it this is valid.
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The following message was posted to: PharmPK
Hi Vishal,
You can do that.
Please check the US-FDA (bioanalytical cross validation section) Guidelines.
Regards,
Sudipta Basu
Senior Research Scientist (DMPK&TOX)
Sai Advantium Pharma Ltd.,
E-Mail : sudipta.b.at.saiadvantium.com
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All,
In such a occasion can we not make matrix mix of Rat plasma: Other(Human?) plasma::1:1 and include the same in validation with a dilution factor of 2 ? (If the sensitivity is good enough!!)
-AB Rao
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Dear Visha,
I can understand your concern about volume of plasma but there are some difference in endogenous components between rat plasma and human plasma. Any how you have to have prove stability(s) in rat plasma. My recent experience suggest enzyme kinetics are different between rat and human plasma. For some of the compounds we observed very high rate of hydrolysis in rat plasma then in human plasma. If someone wants, can raise questions. My suggestion is improve the sensitivity of your assay and reduce the volume of matrix. To avoid higher consumption don't go for bulk spiking in your validation assay.
Regards,
Bhavesh
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