Perspectives in modeling and model validation during analytical quality by design chromatographic method evaluation: a case study

AAPS Open

Table 1 The experimental matrix of the modified CCC design

Run No.	(A) Pump flow rate (mL/min)	(B) Final strong solvent (%)	(C) Oven temperature (°C)	(D) EDTA additive concentration (mM)	Predicted response variance (%)
1^a	0.9	35.0	26.0	0.50	16.67
2^b	0.8	33.0	28.0	0.45	10.80
3^b	1.0	33.0	28.0	0.45	10.87
4^b	0.8	37.0	28.0	0.45	10.87
5^b	1.0	37.0	28.0	0.45	16.67
6^b	0.8	33.0	28.0	0.55	16.85
7^b	1.0	33.0	28.0	0.55	17.02
8^b	0.8	37.0	28.0	0.55	17.02
9^b	1.0	37.0	28.0	0.55	17.21
10^d	0.8	33.0	28.0	0.45	10.80
11^d	1.0	33.0	28.0	0.45	10.87
12^d	0.8	37.0	28.0	0.45	10.87
13^a	0.7	35.0	30.0	0.50	16.91
14^a	1.1	35.0	30.0	0.50	17.14
15^a	0.9	31.0	30.0	0.50	16.91
16^a	0.9	39.0	30.0	0.50	17.14
17^a	0.9	35.0	30.0	0.40	16.67
18^a	0.9	35.0	30.0	0.60	17.41
19^c	0.9	35.0	30.0	0.50	10.00
20^c	0.9	35.0	30.0	0.50	10.00
21^c	0.9	35.0	30.0	0.50	10.00
22^b	0.8	33.0	32.0	0.45	16.85
23^b	1.0	33.0	32.0	0.45	17.02
24^b	0.8	37.0	32.0	0.45	17.02
25^b	1.0	37.0	32.0	0.45	17.21
26^b	0.8	33.0	32.0	0.55	17.32
27^b	1.0	33.0	32.0	0.55	16.16
28^b	0.8	37.0	32.0	0.55	16.16
29^b	1.0	37.0	32.0	0.55	16.16
30^a	0.9	35.0	34.0	0.50	17.41
Parameter ranges	0.7–1.1	33–37	26–34	0.4–0.6

Each run is labeled with the type of design point: ^a, star points; ^b, factorial points; ^c, triplicate replications at the center point (the nominal conditions); and ^d, model robustness points by run 10, 11, and 12, which are the duplicate replications of the factorial points by run 2, 3, and 4, respectively