Validation dilution integrity

Experiment. Two levels of Dilution QC are required. The Dilution QC for dilution integrity is typically at lOx of the High QC. The Dilution QC for dilution linearity should be at a concentration above projected maximum concentration (C ). If the projected Cmix is not available, the recommended concentration would be 50x or lOOx of High QC. To test dilution integrity or linearity, the Dilution QCs need to be diluted at dilution factor (DF) of 10, 50 or 100 to bring the final concentration within the range. It may require multiple steps of dilution. This experiment only needs to be conducted once per each validation. 

In the limit of very dilute solutions, both activity coefficients approach unity so that the activity of A can be replaced by xa, and the activity of B by its molality (assuming that one has chosen molality as the concentration unit). However, as becomes very small the ratio xj jx becomes very large. Thus, in practice, one may not choose the infinitely dilute solution as a reference point but instead a very dilute solution for which Henry s law is valid. Then, integrating equation (1.13.5) between this very dilute concentration designated mj, to any other concentration rrij, one obtains... 

The simplest possible case occurs when (1) both the operating and the equilibrium hues are straight (i.e., there are dilute solutions), (2) Henry s law is valid y /x = yifXj = m), and (3) absorption heat effects are negligible. Under these conditions, the integral term in Eq. (14-20) may be computed by Colburn s equation [Trans. Am. Jn.st. Chem. Eng., 35,211 (1939)] ... 

The application should state the rationale for the design of the in-use stability tests performed. The procedures used should be fully validated. One key factor is that the test should simulate the use of the product as far as practicable. This should include any reconstitution or dilution prior to use. Aliquots should be removed in an appropriate manner following, as far as possible, the usage pattern that will be encountered in practice. Physical (color, clarity, closure integrity, particulate matter, and particulates/particle size), chemical (assays for active ingredient, antioxidants and... 

Human specimens. In our laboratory, we first developed a good laboratory practice (GLP)-validated procedure for quantification of intact rafAON in control human plasma. The rafAON assay validation endpoints were standard curve, between-run precision and accuracy, within-run precision and accuracy, effects of dilution and freeze thaw, stability of rafAON at -80° C, and 4°C in plasma for various times, specificity, integrity of rafAON during plasma sample collection and processing, and lipid interference. The reader is referred to a previous citation for further details (17,27). 

Gap in eqs A2 and A4 is expressed as volume per molecule. These equations are valid for any -component system. Expressions for the Kirkwood—Buff integrals in ternary mixtures can be obtained from eq A4. ° In particular, one can obtain the following expressions for Gu and G23 for an infinitely dilute solute (component 2)... 

The expression (7-189) for the bulk stress is, of course, valid for arbitrary concentrations of particles, but the volume integrals over Vp are exceedingly difficult to evaluate in general because the value for a particular particle depends on the complete configuration of particles in the suspension. For a dilute suspension of identical particles, on the other hand, the problem simplifies immensely, because the integral over Vp is exactly the same for all particles, and the expression (7-189) can be replaced with... 

The use of a UV spectrophotometric procedure can thus be proposed as an alternative method for the determination of inorganic sulphide in water and wastewater. A first method, based on the use of a multiwavelength procedure has been proposed for natural water [35], The interferences are modelled from an exponential function and the simultaneous determination of total sulphide and iodide is possible. A second method integrates the semi-deterministic deconvolution procedure [36]. The potentiometric method will be chosen as reference for the validation of this last procedure. The UV quantification is carried out by deconvolution (see Chapter 2) between 205 nm and 320 nm. Raw samples were diluted four times to prevent the UV signal saturation for a 10-mm quartz cell. Sulphide (HS ) concentration is given by the product of the contribution coefficient of sulphide reference spectrum (replacing nitrate in the previous set) and the corresponding concentration, affected by the dilution factor. 

Procedurally, dilutional linearity should not be confused with the MRD of an assay. The MRD is a designed integral part of an analytical method and involves a predefined dilution of test samples, QC samples and, often, calibrators usually with a buffer-based matrix. In contrast, dilution linearity is used only to support analysis of study samples that exceed the assay s ULOQ and involves dilution(s) intended to result in an analyte concentration within the standard curve s validated range. Another notable difference is that, while MRD is usually performed in buffer, dilutional linearity is performed in matrix, often the same one used to prepare the standard curve. 

If the operating and equilibrium lines are both straight and the solutions dilute, the integral shown in Eq. (10.6-23) is valid. 

Before integration, we assume Henry s law to be valid for this dilute gas stream ... 

The conservation of mass, momentum, and energy can be derived by multiplying the above-specified Boltzmann equation with molecular mass, momentum, and energy, respectively, and then integrating over all possible molecular velocities. Subject to the restriction of dilute gas, the Boltzmann equation is valid for all Kn from 0 to oo. 

By proceeding this way, it is very probable that the result of the integration of the chromatographic peak will be compatible with the use of the validated response function. Proceeding in this manner is legitimate only if one has previously performed tests during method validation to verify that dilution of the sample does not alter the result of the dosage. 

---