Chemistry Reference
In-Depth Information
is encouraged to study the effects of different days, analysts, and equipment on
precision.
The dissolution profiles on the same sample may be run by at least two dif-
ferent analysts, each analyst preparing the standard solutions and the medium.
Typically, the analysts use different dissolution baths, spectrophotometers or
HPLC equipment (including columns), and autosamplers; and they perform the
test on different days.
Acceptance criteria are often calculated from the difference in the mean value
between the dissolution results at any two conditions, and specified to not exceed an
absolute 10% at time points with less than 85% dissolved and not to exceed 5% for
time points above 85%. Acceptance criteria may be product specific, and other sta-
tistical tests and limits may be used. Additional general information on determining
precision can be found in Chapter 4, Section 4.3.2.
7.4.3.5 robustness
The robustness of an analytical procedure is the measure of its capacity to remain
unaffected by small but deliberate variations in parameters internal to the procedure
(Chapter 4, Section 4.3.7; and Chapter 5). For dissolution testing, parameters to be
varied include medium composition (e.g., buffer or surfactant concentration), pH,
volume, agitation rate, and temperature. These parameters would be investigated in
addition to those typically evaluated during validation of the assay method, either
spectrophotometrically or by HPLC.
7.4.3.6 remaining validation tests
In addition to the common analytical performance characteristics normally evalu-
ated for procedure validation, standard and sample solution stability and filter vali-
dation must also be evaluated.
Solution stability is important given the conditions and length of time of some
dissolution tests. The standard and sample solution should be stored under conditions
that ensure stability. Solution stability is analyzed over a specified period of time,
using freshly prepared solutions at each time interval for comparison. The accept-
able range for solution stability is typically between 98% and 102%.
If the solution is not stable, refrigeration may be needed prior to sample analysis,
or protection against photodegradation. A time period for analysis should also be
specified.
Filter validation is accomplished by preparing a suitable standard solution or a
completely dissolved sample solution at the appropriate concentrations. For standard
and sample solutions, the results for filtered solutions (after discarding the appropri-
ate volume) to those for the unfiltered solutions can be compared.
7.5 bIoAnAlytIcAl metHods
Bioanalytical methods are methods that are used for the analysis of drugs and metab-
olites in biological samples, most commonly plasma, urine, or tissues. They are used
in clinical pharmacology, bioavailability, toxicology, bioequivalence, and other stud-
ies that require pharmacokinetic evaluation in support of various drug applications.
