Relative area percent

In addition to targeting specific impurities of interest, the isolation chemist uses SFC for a process Pfizer has termed main band elimination (MBE). This experiment proves useful as a means to enrich low-level impurities when LC-NMR and other structure elucidation experiments are desired. LC-NMR is a technique that proves challenging when impurities are at the less than 1 % level. SFC is a very efficient and fast tool for the removal of the major sample component. This MBE process effectively removes a reaction product from the sample matrix. The resulting sample significantly increases impurity relative area percents allowing for increased loadability and signal intensity for the targeted experiment. 

Off-line HPLC/UV detection is the most common analysis technique used to monitor the disappearance of SM(s) and formation of product(s). " " COR IPC criteria are usually expressed as a relative area percent (RAP) of SM to product. The IPC method should separate all the known impurities from the SM, but not necessarily from the product since minor impurities co-eluting with the product will not significantly affect the IPC result. This approach allows the development of shorter methods. The UV of the SM and/or critical impurities should be used as the HPLC detector setting (if possible) for the... 

Use Normalized Area Percent analysis for impurities and related substances testing. Index the area % to the parent drug (where parent = 100%). Apply a correction for relative response factors (RRF) if those are known. 

The most common technique for monitoring impurities is HPLC with UV detection. Quantification of impurities is achieved by reference standard, when available, or by area percent or height percent relative to the parent compound. Figure 1.4 shows a typical chromatogram enlarged to show the various impurities. One of the impurities is the USP Compound B that is added to the furosemide drug substance. 

Note the area percent shown in Table 9.1.11 is given relative to all identified compounds in the pyrogram. 

Figure 2. Surface response curve showing the level of production of the contaminant P-2, predicted by a statistically designed experimental matrix, as the relative levels of cystine (mM in the initial feedstream pool) and cysteine (mM in the find diluted refold mixture) are varied. P-2 is determined by reversed-phase HPLC, and is expressed as area percent of the chromatogram.

Compound Relative peak area, (percent total peak area)... 

The determination of mole percent 1-hexene in the previous example was based on relative areas measured by spectral integration. The use of peak heights gives mole percents 1-hexene of 2.8 from the 90° data and 2.3 from the -30° data. Relative areas are normally recommended because any difference in resonance line widths will be taken into consideration through a use of relative areas. 

Among the related substances in many antibiotics are various structurally related components in the drug substance, the composite mixture of which is obtained in the synthetic or semisynthetic scheme and which gives rise to the drug efficacy. Control of the relative content of components is therefore necessary for these drugs. Test specification limits for the components are normally stated in terms of area percent of each, as maximum, minimum or a range of values for each or for the sums of several components. The types of components seen in these antibiotics were studied as impurities in the semisynthetic antibiotic clarithromycin, where detection limits of 0.1% w/w were found. Normalization factors were determined for each of 15 known related substances using ratios of the slope of linear calibrations for each substance to that for the reference impurity. 

The surface material was removed by Ar bombardment. The sputtering rates are determined from known thickness of Ta205 films. Since the sputtering rate of this material relative to Ta205 is unknown, the absolute depths are approximate. The relative atomic percents are calculated by using experimental sensitivity factors and peak areas for each of the elements shown. The relative atomic concentrations show reproducibility to 0.2% and are correct to within 5% of the absolute concentrations. 

Variable-Area Flow Meters. In variable-head flow meters, the pressure differential varies with flow rate across a constant restriction. In variable-area meters, the differential is maintained constant and the restriction area allowed to change in proportion to the flow rate. A variable-area meter is thus essentially a form of variable orifice. In its most common form, a variable-area meter consists of a tapered tube mounted vertically and containing a float that is free to move in the tube. When flow is introduced into the small diameter bottom end, the float rises to a point of dynamic equiHbrium at which the pressure differential across the float balances the weight of the float less its buoyancy. The shape and weight of the float, the relative diameters of tube and float, and the variation of the tube diameter with elevation all determine the performance characteristics of the meter for a specific set of fluid conditions. A ball float in a conical constant-taper glass tube is the most common design it is widely used in the measurement of low flow rates at essentially constant viscosity. The flow rate is normally deterrnined visually by float position relative to an etched scale on the side of the tube. Such a meter is simple and inexpensive but, with care in manufacture and caHbration, can provide rea dings accurate to within several percent of full-scale flow for either Hquid or gas. 

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