ISO_NWIPs-for-Ballot

ISO/NP

trueness or systematic error (sensitivity) are assessed using a mass of between 5% and 100% of 614 the balance's capacity; 615 precision or random error (repeatability) is assessed with a mass of approximately 5 % (or less) of 616 the balance's capacity. 617 6.3 Reference materials 618 6.3.1 Reference materials for chemical shift (reference standard) 619 The reference materials for chemical shift are chemical substances that have a frequency that will serve 620 as a reference for determining the chemical shift of the substance to be measured. When a sample 621 solution is prepared in an organic solvent the International Union of Pure and Applied Chemistry 622 (IUPAC) specifies that tetra methylsilane (TMS) shall be used as the reference material. If the sample 623 solution is aqueous, 3-(trimethylsilyl)-1-propanesulfonic acid sodium salt, (4,4-dimethyl-4-silapentane- 624 1-sulfonic acid) (DSS) (TMSP) or(trimethylsilyl propionate carboxylic acid) (TSP) is used in aqueous 625 solvents. In both cases, the resonance position of the signal from these standards is assigned a value of 626 0.000 ppm. 627 6.3.2 Reference materials for qNMR (calibration standard) 628 The reference materials for qNMR are the chemical substances that provide the reference for the purity 629 measurement of the analyte. When a 1 H qNMR analysis is undertaken using a validated method and 630 with a reference material whose purity has been independently established as SI-traceable, the purity 631 value assigned to the analyte will also be traceable to the SI. The assigned material can potentially serve 632 as a secondary, SI-traceable reference material for use in a subsequent qNMR assignment. 633 Currently available CRMs include 1,4-bis(trimethylsilyl) benzene- d 4 (1,4-BTMSB- d 4 ), 3- 634 (trimethylsilyl)-1-propanesulfonic acid- d 6 sodium salt (DSS- d 6 ), maleic acid and dimethyl sulfone. 635 Among these CRMs, there are easy-to-use, solid compounds that provide a sharp single signal at specific 636 chemical shifts near 0 ppm. The ones mainly used as reference materials for qNMR are 1,4-BTMSB- d 4 637 and DSS- d 6 . The former is used with deuterated organic solvents and the latter is used with methanol_ d 4 , 638 dimethyl sulfoxide_ d 6 and deuterated water. 639 In any case, for the reference materials for qNMR, there shall be no mutual interaction in the solvent 640 (such as reaction, decomposition, etc.) between molecules of the analyte compound and the reference 641 materials for qNMR, and the signals used to determine the purity and content shall be completely 642 separated. 643 6.4 Selection of a deuterated solvent 644 Deuterated solvents are used for 1 H qNMR measurements. 645 When selecting a solvent, it is important to establish that the: 646 - signals from the residual non-deuterated solvent do not overlap those from the analyte or the 647 reference material; 648 - both analyte and reference material are sufficiently soluble in the solvent; 649 - solvent does not react with the analyte or reference material 650 It is also important to be aware that the chemical shifts can change due to the influence of factors such 651 as the type of solvent used, the solution concentration and the deuterium ion concentration (pH). In 652 addition, the resolution will decline for a sample solution that has a high viscosity. 653

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