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1、Table 10 (Continued) Standard Solution Concentration of Neu5Ac after Labeling (mM) Concentration of Neu5Gc after Labeling (mM) 40.20.01 50.40.02 Sample solution:Transfer a desalted sample containing approximately 0.550 mg of protein (equivalent to about 5 pmol of sialic acid) into a 0.5-mL microcent
2、rifuge tube. Dry in a vacuum centrifuge without heating. Add 25 mL of 2M acetic acid into the tube and briefly centrifuge to ensure all of the sample is in the well of the tube. Incubate at 80 for 2 h 15 min. NOTEOr use validated sample preparation and time/temperature ranges. Allow the tube to cool
3、 to room temper- ature for approximately 10 min. Then vortex and centrifuge. Label the solution as directed in Labeling before analysis. USP REFERENCE STANDARDS 11 USP N-Acetylneuraminic Acid RS USP N-Glycolylneuraminic Acid RS USP KDN RS 3-Deoxy-D-glycero-D-galacto-2-nonulosonic acid. 1S (USP40) 23
4、2 ELEMENTAL IMPURITIESLIMITS Change to read: INTRODUCTION This chapter specifies limits for the amounts of elemental impurities in drug products. Regardless of the approach used, compliance with the limits specified is required for all drug products unless otherwise specified in an individual monogr
5、aph or specifically excluded in this Introduction. 1S (USP40) Elemental impurities include catalysts and environmental contaminants that may be present in drug substances, excipients, or drug products. These impurities may occur naturally, be added intentionally, or be introduced inadvertently (e.g.
6、, by inter- actions with processing equipment and the containerclosure system). When elemental impurities are known to be present, have been added, or have the potential for introduction, assurance of compliance to the specified levels is required. A risk- based control strategy may be appropriate w
7、hen analysts determine how to assure compliance with this standard. Due to the ubiquitous nature of arsenic, cadmium, lead, and mercury, they (at the minimum) must be considered in the risk assessment. This chapter does not apply to: Radiopharmaceuticals Articles intended only for veterinary use Vac
8、cines Cell metabolites DNA products Allergenic extracts Cells, whole blood, cellular blood components, or blood derivatives, including plasma and plasma derivatives Products based on genes (gene therapy) Cells (cell therapy) Tissue (tissue engineering) Dialysate solutions not intended for systemic c
9、irculation Total parenteral nutritions (TPNs) Elements that are intentionally included in the drug product for therapeutic benefit Dietary supplements and their ingredients, which are addressed in Elemental Contaminants in Dietary Supplements 2232 1S (USP40) The limits presented in this chapter do n
10、ot apply to excipients and drug substances, except where specified in an individual monograph. However, manufacturers of pharmaceutical products need certain information about the content of elemental impurities in drug substances or excipients in order to meet the criteria of this chapter. Drug pro
11、duct manufacturers can use elemental impurity test data on components from tests performed by drug substance or excipient manufacturers, who may provide test data, or if applicable, risk assessments. Elemental impurity data generated by a qualified supplier of drug product components are acceptable
12、for use by a drug product manufacturer to demonstrate compliance with this chapter in the final drug product. Drug substance or excipient manufacturers who choose to perform a risk assessment must conduct that risk assessment using Table 2 in this chapter. Elements that are inherent in the nature of
13、 the material, as in the case of some natu- rally-sourced materials, must be considered in the risk assessment. 1S (USP40) First Supplement to USP 40NF 35Chemical Tests / 232 Elemental ImpuritiesLimits 8065 Official from August 1, 2017 Copyright (c) 2017 The United States Pharmacopeial Convention. A
14、ll rights reserved. Accessed from 10.6.1.1 by yezk3ntgp on Tue May 23 21:15:04 EDT 2017 SPECIATION The determination of the oxidation state, organic complex, or combination is termed “speciation”. Each of the elemental impurities has the potential to be present in differing oxidation or complexation
15、 states. However, arsenic and mercury are of particular concern because of the differing toxicities of their inorganic and complexed organic forms. The arsenic limits are based on the inorganic (most toxic) form. Arsenic can be measured using a total-arsenic procedure under the assumption that all a
16、rsenic contained in the material under test is in the inorganic form. Where the limit is exceeded using a total-arsenic procedure, it may be possible to show, via a procedure that quantifies the different forms, that the inor- ganic form meets the specification. The mercury limits are based upon the inorganic (2+) oxidation state. The methyl mercury form (most toxic) is rarely an issue for pharmaceuticals. Thus, the limit was established assuming
