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abstract
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nation of ilaprazole and its related impurities in commercial tablets was developed and
validated. The chromatographic separation was carried out by gradient elution using an
31 August 2014
Agilent C8 column (4.6 mm 250 mm, 5 mm) which was maintained at 25 C. The mobile
phase composed of solvent A (methanol) and solvent B (solution consisting 0.02 mmol/l
monopotassium phosphate and 0.025 mmol/l sodium hydroxide) was at a flow rate of
1.0 ml/min. The samples were detected and quantified at 237 nm using an ultraviolet
Keywords:
absorbance detector. Calibration curves of all analytes from 0.5 to 3.5 mg/ml were good
Ilaprazole
linearity (r 0.9990) and recovery was greater than 99.5% for each analyte. The lower limit
Enteric-coated tablets
of detection (LLOD) and quantification (LOQ) of this analytical method were 10 ng/ml and
Related impurities
25 ng/ml for all impurities, respectively. The stress studies indicated that the degradation
HPLC
products could not interfere with the detection of ilaprazole and its related impurities and
Validation
the assay can thus be considered stability-indicating. The method precisions were in the
range of 0.41e1.21 while the instrument precisions were in the range of 0.38e0.95 in terms
of peak area RSD% for all impurities, respectively. This method is considered stabilityindicating and is applicable for accurate and simultaneous measuring of the ilaprazole
and its related impurities in commercial enteric-coated tablets.
2015 Shenyang Pharmaceutical University. Production and hosting by Elsevier B.V. This is
an open access article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/).
1.
Introduction
* Corresponding authors. Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Tel.: 86 24 23986293/
6325; fax: 86 24 23986293/6325.
E-mail addresses: xulu1974@hotmail.com, LVJ221@163.com (L. Xu).
Peer review under responsibility of Shenyang Pharmaceutical University.
http://dx.doi.org/10.1016/j.ajps.2014.09.001
1818-0876/ 2015 Shenyang Pharmaceutical University. Production and hosting by Elsevier B.V. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
a s i a n j o u r n a l o f p h a r m a c e u t i c a l s c i e n c e s 1 0 ( 2 0 1 5 ) 1 4 6 e1 5 1
147
Fig. 1 e Chemical structures of (A) ilaprazole, (B) ilaprazole sulfur ether and (C) ilaprazole sulphone.
Chemistry Lab of Shenyang Pharmaceutical University (Shenyang, China). HPLC-grade methanol was from Fisher Scientific Worldwide (Shanghai) Co., Ltd. (Shanghai, China).
Deionized-distilled water was used throughout this study.
All other reagents were of analytical grade.
2.2.
2.3.
2.
2.1.
Materials
148
a s i a n j o u r n a l o f p h a r m a c e u t i c a l s c i e n c e s 1 0 ( 2 0 1 5 ) 1 4 6 e1 5 1
2.4.
2.5.
2.5.1.
Acid degradation
2.5.2.
Alkali degradation
2.5.3.
Oxidative condition
2.5.4.
2.5.5.
Photostability study
3.
3.1.
3.2.1.
3.2.2.
Specificity
3.2.3.
The LOQs for ilaprazole impurity A, B, C, D, E, ilaprazole sulphone and ilaprazole sulfur ether corresponding to a signalto-noise ratio of 10 were 25 ng/ml, 200 ng/ml, 75 ng/ml,
125 ng/ml, 750 ng/ml, 200 ng/ml and 200 ng/ml, respectively.
149
a s i a n j o u r n a l o f p h a r m a c e u t i c a l s c i e n c e s 1 0 ( 2 0 1 5 ) 1 4 6 e1 5 1
Fig. 3 e Chromatograms of stress test. (A) Untreated tablet powders; (B) acid hydrolysis-degraded tablet powders; (C) base
hydrolysis-degraded tablet powders; (D) dry-heated tablet powders; (E) light degraded tablet powders; (F) oxidation
degraded tablet powders (the peak number is the same as in Fig. 2).
3.2.4.
3.2.5.
Linearity
Precision
Regression equation
147.39C 5162.7
84.09C 2570.1
95.128C 2427.7
102.61C 2903.1
14.371C 701.86
70.984C 2730.1
0.9997
0.9999
0.9996
0.9999
0.9994
0.9992
A 107.66C 3309.3
0.9990
A
A
A
A
A
A
Correlation
coefficient (r)
Impurity A
Impurity B
Impurity C
Impurity D
Impurity E
Ilaprazole sulphone
Ilaprazole sulfur ether
Method
precision
RSD (%)
Instrument
precision
RSD (%)
0.41
0.69
1.09
0.85
1.21
0.71
0.68
0.38
0.44
0.85
0.42
0.95
0.51
0.78
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a s i a n j o u r n a l o f p h a r m a c e u t i c a l s c i e n c e s 1 0 ( 2 0 1 5 ) 1 4 6 e1 5 1
Added (mg/ml)
Found (mg/ml)
Recovery (%)
RSD (%)
0.80
1.00
1.20
0.80
1.00
1.20
0.80
1.00
1.20
0.80
1.00
1.20
0.80
1.00
1.20
0.80
1.00
1.20
0.80
1.00
1.20
0.80
1.00
1.20
0.80
1.00
1.21
0.80
1.00
1.20
0.80
1.00
1.19
0.81
1.00
1.21
0.81
1.00
1.21
0.80
1.00
1.20
99.8
99.9
99.7
100.5
100
100.5
100.2
100.3
100.2
100
99.8
99.5
100.5
99.8
100.4
100.9
100.3
100.9
99.7
100
99.8
0.54
0.31
0.98
1.08
0.86
0.82
0.28
0.32
0.43
0.70
0.49
0.43
1.21
0.45
0.96
0.42
0.16
0.51
1.19
0.94
0.88
99.8
0.61
100.3
0.92
100.2
0.34
99.8
0.54
100.2
0.87
100.7
0.37
99.8
1.01
Impurity A
Impurity B
Impurity C
Impurity D
Impurity E
Ilaprazole sulphone
3.2.8.
3.2.6.
Accuracy
3.2.7.
Stability
Ambient
temperature
4 C
4h
6h
8h
10 h
12 h
2.91
4.44
6.79
8.87
11.01
13.40
1.84
3.13
5.50
5.64
7.78
10.17
Robustness
The robustness of the HPLC method was studied under a variety of conditions including changes of flow rate and the
proportion of buffer and organic phase. The small deliberate
variations of these parameters were not significantly affected
the reproducibility of the proposed method, which proved
good robustness of the HPLC method.
4.
Conclusions
Impurity A
Impurity B
Impurity C
Impurity D
Impurity E
Ilaprazole
sulphone
Ilaprazole
sulfur ether
4h
6h
8h
10 h
12 h
0.67
0.56
0.22
0.54
0.70
0.65
0.97
0.34
0.06
0.54
0.11
0.35
0.38
0.59
0.77
0.92
0.87
0.60
0.30
0.89
0.78
0.79
0.08
0.21
0.77
0.98
0.76
0.77
0.82
0.27
0.45
0.37
0.66
0.59
0.31
0.50
0.57
0.45
0.59
0.24
0.26
0.47
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Table 6 e Results of stability of the stock solutions of different impurity at 4 C for four weeks.
Compound
Rate of change (%)
Impurity A Impurity B Impurity C Impurity D Impurity E Ilaprazole sulphone Ilaprazole sulfur ether
0.48
0.17
0.41
0.39
references
0.64
0.37
0.85