Dr. KnowAllowed changes in LC Methods acc. USP 34, Section 621 (Updated 2022)
| Parameter | Isocratic Methods | Gradient Methods |
| pH | ±0.2 | ±0.2 |
|---|---|---|
| Buffer Concentration | ±10% | ±10% |
| Mobile Phase/ Gradient Volume |
Solvent ratio up to the lesser of ±±30% relative or ±10% absolute for minor components |
Gradient segments adjusted according to the equation: tG2 = tG1 × (F1 / F2) × (L2 × dc2²) / (L1 × dc1²) |
| UV Wavelength | No changes allowed | No changes allowed |
| Column Length and Particle Size |
Length, L × particle diameter, dp = −25% to +50% or (tR/w0.5)² = −25% to +50% when changing from fully porous to superficially porous silica |
As per isocratic methods with a requirement that selectivity and elution order are equivalent to the original monograph parameters for controlled impurities |
| Stationary Phase | Change allowed provided USP column classification (L1, L7, L11, etc.) is maintained | Change allowed provided USP column classification (L1, L7, L11, etc.) is maintained |
| Column Diameter | Allowed | Allowed |
| Flow Rate |
OK, if column performance (efficiency) does not reduce by >20% Adjust according the equation: F2 = F1 × (dc2² × dp1) / (dc1² × dp2) |
Adjust according the equation: F2 = F1 × (dc2² × dp1) / (dc1² × dp2) |
| Injection Volume |
Adjust according the equation: Vinj2 = Vinj1 × (L2 × dc2²) / (L1 × dc1²) |
Adjust according the equation: Vinj2 = Vinj1 × (L2 × dc2²) / (L1 × dc1²) |
| Column Temperature | ±10 K | ±5 K |
Allowed changes in GC Methods acc. USP 34, Section 621 (Updated 2022)
| Stationary phase | |
|---|---|
| Particle size | Maximum reduction of 50%; no increase permitted (packed columns) |
| Film thickness | −50% to +100% (capillary columns) |
| Column dimensions | |
| Length | −70% to +100% |
| Internal diameter | ±50% |
| Column temperature | ±10% |
| Temperature program | Adjustment of temperatures is permitted as stated above; adjustment of ramp rates and hold times of up to ±20% is permitted |
| Flow rate | ±50% |
| The above changes are acceptable provided system suitability criteria are fulfilled and selectivity and elution order of the specified impurities to be controlled are demonstrated to be equivalent | |
| Injection volume and split ratio | May be varied provided system suitability criteria remain within their established acceptability limits. When the injection volume is decreased, or the split ratio is increased special attention is given to (limit of) detection and repeatability of the peak response(s) to be determined. An increase in injection volume or decrease in split ratio is permitted provided, in particular, linearity and resolution of the peak(s) to be determined remain satisfactory |
| Injection port temperature and transfer-line temperature in static headspace conditions |
±10° C, provided no decomposition or condensation occurs |