Chromatography Forum

We have one issue with our “ micro balanceâ€

To weigh 2 mg with a relative repeatability of 1% you need a balance that weighs to better than 20 micrograms. In practise this means a five figure or six figure balance. To eliminate bias you have to calibrate the balance using calibrated (traceable) weights.

Your hands on technique and the environmental conditions in the weighing room will be as important as the repeatability and resolution of the balance itself.

The best way to estimate the repeatability of your weighings is to do multiple replicates.

Check out the articles by Burgess and McDowall in LC-GC Europe:

http://www.lcgceurope.com/lcgceurope/ar ... goryId=541

http://www.lcgceurope.com/lcgceurope/ar ... ?id=311444

Peter

You'll have to weigh more and dilute accordingly. This will be more defendable than weighing a standard amount below the USP's definition of "accurately weighed" for your balance (which is what you would be doing if you follow your suggested procedure). If you can't make use of more than 2mg, you need a balance that can weigh 2mg with a stdev (n=10) low enough that 3*(stdev)<0.001.

In other words, the importance lies in the differences in weights that your balance can handle [(sample + container...) - container]. Also, the more non-sample weight (container, etc.) you put on a balance the higher the weighing inaccuracy.

iirc the minimum weigth for a balance as per USP is defined for assay only and does not apply for impurities. I would check that out.
Just adding some Tara to get into the minimum weight criteria is not a good idea.

Alex

We are aware of all these USP criteria and accordingly min and max weighing capacity of this Microbalance is established.

Ideally we should have a balance with measurement uncertainty satisfactory below 2 mg or so. But the argument with-in our group is as follows,

The weighing is not related to what we weigh i.e. the container plus sample is well with-in the acceptable range of this microbalance. In other words we are weighing 5 mg (container) and 7 mg (container +impurity standard). The accuracy in both cases is acceptable as per USP than why cant we take difference between the two (2 mg) accurate also??

Alex: USP talk about Assay and this could be assay of anything including impurities. Interestingly USP has two criteria for balance,
1.measurement uncertainty (random plus systematic error) does not exceed 0.1% of the reading. (Does not conform)
2.Measurement uncertainty is satisfactory if three times the standard deviation of not less than ten replicate weighing divided by the amount weighed, does not exceed 0.001 (conform).

I am wondering what is the industry practice??

JM

I like the topic ya'll, good stuff!

1. I agree the best option is to increase the weight of your impurity
and dilute accordingly. You will be using a weight that is within
the specs of the balance estableshed during the instrument
qualification. You should also make sure that the weight is within spec
of your scheduled calibration, and daily balance check.

2. If I'm understanding the problem correctly - the method specifies
to use 2mg, that's the reason for wanting to weigh 2g. You can
safely adjust your sample weight accoringly and dilute and not be
deviating from the method - the only requirement is that your final
concentration is the method concentration (i.e. concentration used
during validation).

3. Using an instrument outside the specs set forth by calibration
/instrument qualification is a big "no no" and could be a finding by
the regulatory agency.

4. I think that using 2 weights within spec and subtracting the two
to get a weight outside the inst. specs is still using the instrument
outside it's specs. There's an uncertaintanty associated with each
weight - and the two combined can be greater than 0.1%.

That's what I think!

Thank you all,

Hi brian !! let me clarify here that this is not a problem ( i know how to go about as indicated by you all ) but a thought provoking question and the argument i also fell for,

[/quote]Using an instrument outside the specs set forth by calibration
/instrument qualification is a big "no no" and could be a finding by
the regulatory agency.

Am I weighting out side the spec? the ans is NO as i am weighting 5 mg and 7 mg both are within the spec.

regarding 2 weights , common practice " place paper or container "tare" add sample "tare" transfer the sample , put back the container = read the weight " you see how many times " weighing is done? if this is accurate why not mine?

JM

But the argument with-in our group is as follows,
The weighing is not related to what we weigh i.e. the container plus sample is well with-in the acceptable range of this microbalance. In other words we are weighing 5 mg (container) and 7 mg (container +impurity standard). The accuracy in both cases is acceptable as per USP than why cant we take difference between the two (2 mg) accurate also??

Joking aside -
Your balance doesn't "weigh by difference" any more accurately than it weighs post-tare. As HW said, if your vessel adds enough mass to the pan, especially on a balance that changes ranges (& specs) automatically, you may be even farther from compendial dictum. Remember, all balances do is discriminate between 2 conditions. The higher the ratio of vessel mass : material mass gets, the less accurate it will be. (Have you ever heard the line about using the Queen Mary to hold & weigh deck chairs).

There is more than enough readily available material about good practise in weighing for this general type of argument to be settled.

Nonetheless, this specific discussion is not going to get to a conclusion by philosophising. Let's make like Galileo and Newton and do some experiments.

JM - using your usual procedure of weigh empty container, weigh full container, subtract for weight of content, do replicate weighings on a solid object that weighs 2 mg, preferably a certified weight so that when you post the results on the forum we can see both the repeatability and the bias. If you can accurately weigh 2 mg you could argue that the 3 mg lower limit on the balance was too conservative.

HW Mueller and DR, I think that you will be surprised by the ability of top end microbalances to accurately weigh small differences even with a heavy weight on the pan. Try it with no weight, 1/3 of the balance's capacity and 2/3. In other words, weigh a small weight on an empty pan, remove the small weight and add say 20 g if the balance capacity is 60 g, then add the small weight and see what the difference is.

Peter

What is the resolution of this balance, that is the smallest difference that it can display? If you try to weigh too close to the minimum quantization, you will get an artificially low %RSD.

There is a feature in some balances that treats any measurement below a certain threshold as noise, and such measurements are autozeroed whether you like it or not. Is that the reason for the >3mg requirement? (The feature can be turned off.)

When we had our balances certified by the Mettler technician, he did check the linearity and precision for small differences at low, middle and high load. The spec is the same across the entire range. If you ever get a chance to watch it done, you will learn something about your balance.

The B.S. meter is a classic...

Stay classy San Diego!

I hope the original poster has found an appropriate solution, sadly I suspect they will have to weigh more if they want to comply with USP.

It's also worth noting that the USP has ( or soon will ) significantly changed the rule regading calibration of the balances. I don't have access to the 2006 edition to check if Section 41 has already changed, but the USP is planning on bringing their requirements into line with NIST, and many more user and calibration checks will be included. Section 41 is a mandatory requirement for USP work.

The proposal included several changes eg. Use of 2 significant figures for the expanded uncertainty ( 0.10% instead of 0.1% ). More frequent determination of the repeatability Std Dev, using multiple users and different environments/times. Verifying linearity and span accuracy using five test points with calibrated masses. Determining minimum permissible weight to achieve the 0.10% uncertainty by using a control chart derived from routine weighing.

Inevitably, I suspect many balances will have the minimum weighable quantity increased, so people developing/using "accurately weighed" USP methods ( includes all assays and most related substances ) should ensure they specify suitable sample weights in any chromatographic procedures.

Bruce Hamilton

Check out the articles by Burgess and McDowall in LC-GC Europe:

http://www.lcgceurope.com/lcgceurope/ar ... goryId=541

http://www.lcgceurope.com/lcgceurope/ar ... ?id=311444

Peter, do you have the first article? Thank you.

Peter, Mark,
there is no surprise at all regarding accuracy at different weights, I use balances often ..... since the days of two pan swings. It is theory, not philosophy. There is no way, even with a modern electronic balance to increase the weighing accuracy by adding crab (and increasing accuracy that way was suggested by JM!!). The fact that there are balances for the different ranges pays tribute to the relationship of accuracy and mass, and probably also to the fact that a certain mechanism is optimum. Thus, even if boyancy plays a role you can compensate for it, and you are back to this relationship.
(DR. I was thinking of putting an elephant...)