USP Minimum Sample Weight

Minimum sample weight is defined as the minimum sample quantity required by a balance or scale to obtain a reliable result, taking into account factors such as measurement uncertainty. In the pharmaceutical industry, the United States Pharmacopoeia (USP) is widely recognized as the official authority that prescribes the requirements for determining minimum sample weight.

According to USP Chapter <41> Weights and Balances ⁱ, measurement uncertainty should satisfy the following requirements:

1. The measurement uncertainty of a balance or scale does not exceed 0.1% of the reading.
2. Three times the standard deviation ⁱⁱ, as determined by at least 10 replicate weighings, does not exceed 0.001 (0.1%) when divided by the amount weighed.

The conditions above can be expressed using the following equations:

Resolution	Model	Capacity	Repeatability (σ)	Measurement Uncertainty (3σ)	Minimum Sample Weight
0.01mg	GH-202	51g (Fine range)	0.02mg	0.06mg	60mg
	GR-202	42g (Fine range)
0.1mg	GH-200	220g	0.1mg	0.3mg	300mg
	GR-200	210g
0.001g	GX-200	210g	0.001g	0.003g	3g
0.01g	GX-2000	2100g	0.01g	0.03g	30g

Comparison of Matrix Effects in HPLC-MS/MS

Jet C. Van De Steene and Willy E. Lambert

Laboratory of Toxicology, Ghent University, Ghent, Belgium

When developing an LC-MS/MS-method matrix effects are a major issue. The effect of

co-eluting compounds arising from the matrix can result in signal enhancement or suppression.

During method development much attention should be paid to diminishing matrix

effects as much as possible. The present work evaluates matrix effects from aqueous

environmental samples in the simultaneous analysis of a group of 9 specific pharmaceuticals

with HPLC-ESI/MS/MS and UPLC-ESI/MS/MS: flubendazole, propiconazole, pipamperone,

cinnarizine, ketoconazole, miconazole, rabeprazole, itraconazole and domperidone. When

HPLC-MS/MS is used, matrix effects are substantial and can not be compensated for with

analogue internal standards. For different surface water samples different matrix effects are

found. For accurate quantification the standard addition approach is necessary. Due to the

better resolution and more narrow peaks in UPLC, analytes will co-elute less with interferences

during ionisation, so matrix effects could be lower, or even eliminated. If matrix effects

are eliminated with this technique, the standard addition method for quantification can be

omitted and the overall method will be simplified. Results show that matrix effects are almost

eliminated if internal standards (structural analogues) are used. Instead of the time-consuming

and labour-intensive standard addition method, with UPLC the internal standardization can

be used for quantification and the overall method is substantially simplified. (J Am Soc Mass

Spectrom 2008, 19, 713–718) © 2008 American Society for Mass Spectrometry