Primary reference standard

Most currently used oxidant and ozone monitors need to be calibrated with a predetermined concentration of ozone in air. Regardless of the principle used to measure ambient ozone or oxidant concentrations, the primary reference standard for calibrating each monitoring device or system should be identical everywhere. This requirement remains to be achieved in practice. Up to June 1975, at least seven calibration procedures were practiced in the United States. These are listed in Table 6-5... 

TABLE 6-5 Primary Reference Standards for Calibration of Ozone or Oxidant Analysis... 

Accuracy- agreement with respect to a primary reference standard. 

Accuracy with respect to primary reference standard Not specified... 

The fundamental factors that govern the accuracy of primary reference standards are discussed in this chaptw. Even though an improved reference standard has been advocated, most of the existing air monitoring and laboratory-exposure data have as their reference the potassium iodide procedure used by either the carb, the laapcd, or the EPA. The relationship of these three variations of the potassium iodide procedure to the ultraviolet method is as follows ... 

There is a range of standards for hydrogen isotopes. The primary reference standard, the zero point of the 5-scale, is V-SMOW, which is virtnally identical in isotopic composition with the earlier defined SMOW, being a hypothetical water sample orginally defined by Craig (1961b). 

Gradient RP-HPLC separation with 0.1% formic acid and methanol as mobile phase components (0.25 mL/min) combined either with ESI-time-of-flight [23] MS detection or with chemiluminescence nitrogen detection (CLND) was used to identify and, respectively, quantify illicit drugs in seized material without primary reference standards [24], The method exploits the accurate mass measurement provided by TOE MS, enabling the unequivocal identification of molecular formula of the unknown analyte, and the CNLD equimolar response to nitrogen. 

The functional group which produces the observed band, The multiplicity of the band is indicated in parenthesis s = singlet m = complex multiples Primary reference standard for room temperature and below. 

The primary reference standard is normally prepared on a laboratory scale using pure starting materials, reagents, and solvents and should be of the highest purity that reasonably can be obtained. The synthetic procedure used to make it and the method(s) used for its purification, also should be provided. (If applicable, the method of manufacture section can be referenced.) The purification procedure is normally performed until little or no change is observed through two consecutive cycles in assay purity and levels of impurities. 

Reference Standard. Characterization and structure elucidation data are typically derived from tests conducted on the primary reference standard. Its suitability must be documented by information much more extensive than prescribed in the specifications. In addition to the prescribed analyses—especially levels of impurities—other tests normally conducted include elemental analysis and ultraviolet, infrared, nuclear magnetic resonance, and mass spectrometry, along with reviews of each providing assignments of the important features supporting the structure(s) of the drug substance. Other tests such as... 

Primary reference standard for room temperature and below. 

Primary reference standard of the active compound. The standard of an active compound is typically comprehensively characterized. Table 3 lists the detail required. 

Related compound standard. These standards are typically characterized fully, but not to the same extent as the primary reference standard of the active... 

A detailed qualification report is drafted for a primary reference standard of the active compound less comprehensive documentation is typical of the other standards. Portions of this report may be submitted to the regulatory authorities. The report references the synthetic route for the standard and any purification schemes that were utilized in preparing the pure standard. Other components of this report may include the following ... 

Reference standard, secondary A substance of established quality and purity, as shown by comparison with a primary reference standard, used as a reference standard for routine laboratory analysis. 

Secondary laboratory reference standards (e.g., production lots that are further purified and qualified in the laboratory) should be appropriately prepared, identified, stored, and tested, as necessary, to ensure their suitability for use. The suitability of each lot of secondary reference standard should be determined prior to use by comparing against a primary reference standard obtained from an official source and periodically requalifying each lot in accordance with a written protocol. Primary reference standards need not be tested if stored under conditions consistent with those described in the labeling. 

PRIMARY REFERENCE STANDARD A particular portion, lot or batch of an API or intermediate that has been shown by an extensive set of analytical tests to be of the highest purity. This standard may be purchased from a recognized source or may be prepared by independent synthesis or by further purification of existing production material. 

Method of preparation— The preparation of the primary reference standard for the API should be provided, with a focus on the means of purification. The synthesis used to manufacture the batch can be summarized, or referenced to another section of the application, as appropriate. 

Characterization data—Full characterization data should be supplied for the primary reference standard, including the results from analytical testing and spectral characterization. The assigned purity of the reference standard should be clearly designated. 

Laks, S., A. Pelander, E. Vuori, E. Ali-Tolppa, E. Sippola, and I. Ojanpera. 2004. Analysis of street drugs in seized material without primary reference standards. Anal. Chem. 76 7375-7379. 

Related compound standard These standards are typically characterized fully, but not to the same extent as the primary reference standard of the active drug substance. Because quantities of these standards are typically limited, response factors for these standards can be assigned to eliminate routine use in FIPLC purity determination. 

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