Chemistry Reference
In-Depth Information
tAble 9.1
summary of precision and system suitability results for an Hplc stability
Indicating Assay with two Active Ingredients and two degradation products
Avg.
Area
%rsd
Area
Avg.
rt.
%rsd
rt.
Avg.
rs.
%rsd
rs.
Avg.
n
%rsd
n
component
NTAP
298826
0.5
1.926
0.2
—
—
1291
0.9
ACBS
239073
0.5
2.622
0.1
3.92
0.286
5748
1.2
HCT
642003
1.0
2.889
0.1
1.97
0.416
7149
1.2
TMT
1018352
0.8
4.535
0.1
11.77
0.499
17997
1.4
Note:
Triamterene (TMT) and hydrochorothiazide (HCT) are the active ingredients, while 5-nitroso-2,4,6-
triaminopyrimidine (NTAP) and 4-amino-6-chloro-1,3-benzenesulfanamide (ACBS) are the
related substances called out in the compendial procedure. Average of six replicates at 0.63 mg/mL
each. Rt. is retention time, Rs. is resolution, and N is efficiency or plates.
tAble 9.2
verification of the Quantitation limit
level 1
response
level 2
response
level 3
response
level 4
response
level 5
response
1
8164
13585
21296
42395
61740
2
8130
13785
20936
42467
63528
3
8734
13195
21220
41976
62152
Mean
8343
13522
21151
42279
62473
STDev.
339.3
300.0
189.8
265.1
936.3
Average standard deviation:
406.1.
Slope of calibration curve:
4760000.
Calculated quantitation limit:
0.00085 mg/mL.
The quantitation limit was calculated according to established USP and ICH
guidelines by the formula:
QL = 10STD/S, where STD is the average standard
deviation of the response and S is the slope of the calibration curve [14].
9.5 Implement An exIstIng stAndArd
metHod WItH AdJustments
When implementing an existing standard method with adjustments, the main thing
to keep in mind is that as long as the adjustments are within system suitability guide-
lines (Chapter 5) or within the bounds of a robustness study (Chapter 5), it is not
necessary to perform a revalidation. According to the ORA guideline, the modified
procedure should not adversely affect the precision and accuracy of the data gener-
ated as measured against the performance specifications of the method [3].
Changes in column length, diameter, and particle size fit into this category, and
additional USP guideline revisions are under way to accommodate the implementation
