If adjustments are made to a pharmacopeial procedure, additional verification tests may be required.
To verify the suitability of the adjusted pharmacopoeial procedure, assess the relevant analytical
performance characteristics potentially affected by the change.
When a pharmacopeial procedure has been adjusted according to the requirements stated below, no
further adjustments are allowed without appropriate revalidation.
Compliance with the system suitability criteria is required to verify that conditions for satisfactory
performance of the test or assay are achieved.
Adjustment of conditions with gradient elution (HPLC) or temperature programming (GC) is more
critical than with isocratic (HPLC) or isothermal (GC) elution, since it may shift some peaks to a different
step of the gradient or to different elution temperatures, potentially causing partial or complete coelution
of adjacent peaks or peak inversion, and, thus leading to the incorrect assignment of peaks and to the
masking of peaks or a shift such that elution occurs beyond the prescribed elution time.
For some parameters the adjustments are explicitly defined in the monograph to ensure the system
suitability.
Thin-Layer Chromatography
Composition of the mobile phase: the amount of the minor solvent components may be adjusted by
±30% relative or ±2% absolute, whichever is the larger; no other component is altered by more than
10% absolute. A minor component comprises less than or equal to (100/n)%, n being the total number of
components of the mobile phase. For a minor component at 10% of the mobile phase, a 30% relative
adjustment allows a range of 7%–13% whereas a 2% absolute adjustment allows a range of 8%–12%,
the relative value therefore being the larger; for a minor component at 5% of the mobile phase, a 30%
relative adjustment allows a range of 3.5%–6.5% whereas a 2% absolute adjustment allows a range of
3%–7%, the absolute value being the larger in this case.
pH of the aqueous component of the mobile phase: ±0.2 pH units, unless otherwise prescribed
Concentration of salts in the buffer component of a mobile phase: ± 10%
Application volume: 10%–20% of the prescribed volume if using fine particle size plates (2–10 µm)
Liquid Chromatography: Isocratic Elution
Stationary phase: No change of the identity of the substituent (e.g., no replacement of C18 by C8);
the other physicochemical characteristics of the stationary phase, i.e., chromatographic support, surface
modification and extent of chemical modification must be similar; a change from totally porous particle
(TPP) columns to superficially porous particle (SPP) columns is allowed provided the above-mentioned
requirements are met.
Column dimensions (particle size, length): The particle size and/or length of the column may be
modified, provided that the ratio of the column length (L) to the particle size (dp) remains constant or in
the range between −25% to +50% of the prescribed L/dp ratio.
Adjustments from totally porous to superficially porous particles: For the application of particle-size
adjustment from totally porous to superficially porous particles, other combinations of L and dp can be
used, provided that the plate number (N) is within −25% to +50%, relative to the prescribed column.
These changes are acceptable, provided that system suitability criteria are fulfilled, and selectivity and
elution order of the specified impurities to be controlled are demonstrated to be equivalent.
Internal diameter: In absence of a change in particle size and/or length, the internal diameter of the
column may be adjusted.
Caution is necessary when the adjustment results in smaller peak volumes due to a smaller particle
size or smaller internal column diameter, a situation that may require adjustments to minimize extra-