accepting a batch standards and QC's after preparation

[hombie]

Dear all

In my lab we analyse drugs in human plasma samples by Hplc, UPLC, GC and LCmsms. For all the drugs we investigate, we prepare a batch (in human plasma) of Std's and QC’s our selfs and store them in a freezer (the stability has been checked of course). Methods are always validated by FDA guidelines.

My questions is: Is there rule or guideline available for preparing self/home made standards and QC’s and accepting them after preparation?

In our lab, when a new batch of std and qc’s are made, they will be measured in duplicate and calculated with the present (stable) standards. The “accept criteria” for a new standard or QC is +/- 5% of it’s spiked value.

In my opinion the window +/-5% is sometimes to close and is more of a “house rule” in our lab.

When the accuracy and precision of a method for instance is large (for instance >5%). The risk of rejecting new made standards an qc is more likely than, accuracy and precision of a method with 2%.

What we are doing now is sometimes measuring, measuring eventually got lucky?

I hope that someone could help me..

[BHolmes]

First off, +/-5% is an unrealistic criteria - the LC variation can be +/-5% by itself!

I work as a chemist for the Pesticide Database Program, a national pesticide residue database program that operates through cooperative agreements between State agriculture departments and other Federal agencies. Most, or all the participating departments make their own standards like you described. To ensure accuracy between all labs we are required to participate in a 3rd party proficiency testing, we are also encouraged to make our own internal QCs for additional proficiency testing (our lab does). So all in all, we have around 4-5 annual QCs to confirm the accuracy of our standards and testing methods. I highly suggest looking into a suitable proficiency testing program that meets your needs, just make sure they are ISO accredited.

As for your question

Is there rule or guideline available for preparing self/home made standards and QC’s and accepting them after preparation?

I would first suggest looking towards any certification that you lab may have (A2LA, FDA, etc...) and use their guidelines. For the Pesticide Data Program there are a set of standard operating procedures that all participating departments/agencies must follow and abide by. All can be found here: http://www.ams.usda.gov/AMSv1.0/ams.fet ... tcddataprg
To summarize: for any of our single analyte standards, they must match within 15% relative percent difference (RPD), this is for ALL participating labs. For any of our mixed analyte standards, the duplicate new standards must match within 20% RPD and the old-new standards should match within 20% RPD but due to the fact that some of our analytes degrade before the new mix is made this cannot be met sometimes. So long as the duplicate new mixed standards match and we can show that the failed analyte has failed in the past (we must keep records for 5 years to document these poor integrities), the mix is cleared for use.

These limits were loosely based upon the Horwitz Equation http://www.rsc.org/images/horwitz-funct ... 214859.pdf, however it has been discussed that the use of Horwitz to estimate uncertainties is not suitable for ISO 17025.

Another common method to determine uncertainty of measurements is to conduct a Gauge Repeatability and Reproducibility study. First introduced in the automobile industry it is an exhaustive study that investigates the effects of different lots of materials, different operators, different instruments, different analysis dates, etc... (basically all variables in a given process) on the final result.

Hope this helps.

[hombie]

Bholmes, Thanks for your reaction!

I totally agree that: “+/-5% is an unrealistic criteria - the LC variation can be +/-5% by itself!”

For some HPLC-UV detections it will work (especially with one drug component in a assay).. For LC-MS we use 10% (what also works in my opinion) Never the less…it’s difficult to convince my colleagues that +/- 5% tolerance is not the best way for many of our assays.

I was thinking to do something with validation parameters, such as accuracy and precision on inter and intra day variations.
We also use sheward cards of our “home made” QC’s, to notice any trends. This data also can be used to set up criteria. I think?

We are participating with different kind of 3rd proficiency testing programs. When we make new std’s and qc’s, sometimes we use old proficiency test samples as an extra check.

We also try to get an ISO 15189 certification. ISO 15189 doesn’t say what kind of criteria it must confirm.

Thanks for your reply! Sometimes it’s nice to see ideas of other kind of laboratory practices

( sorry for my misspellings and grammar errors…I don’t write a lot in English)