Integrated Application of Risk Management Techniques in Developing an Analysis Method for Traditional Chinese Medicine: A Case Study of a Percolation Solution for Xiaochaihu Capsules
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Preparation of Sample Solution
2.3. Preparation of Standard Solution
2.4. Risk Management Process throughout the Entire Lifecycle of the Analytical Method
2.5. Preliminary Screening of CMPs through Single-Factor Experiments
2.6. Experimental Design
2.7. Data Processing
2.8. Control Strategy Formulation
3. Results and Discussion
3.1. Determination of ATP
3.2. The Ishikawa Diagram Analysis
3.3. Preliminary FMEA Risk Assessment
3.4. Results of the Preliminary Experiments
3.4.1. Selection of the Detection Wavelength
3.4.2. Selection of the Chromatographic Column
3.4.3. Selection of the Mobile Phase System, Flow Rate, and Initial Gradient
3.4.4. Selection of Column Temperature
3.4.5. Selection of the Centrifugal Concentration Temperature
3.4.6. The Selection of Reconstitution Solvent and Volume
3.5. Results of the CCD
3.6. Data Modeling
3.7. Development and Verification of the MODRs
3.8. Risk Review Based on the Robustness and Verification Experiment Results
3.9. Results of Methodological Validation
3.10. Control Strategy
3.11. Application of the Method
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Element | Targets |
---|---|
Intended purpose | Determination of four target compounds in GGPP |
Analysis object | GGPP |
Main characteristic of the analysis object | There are multiple types of components, and the chemical structures of most components are unclear. |
Quantitatively detected compounds | Uridine, adenine, guanosine, and 5-hydroxymethylfurfural |
Analytical method performance requirements |
|
Attribute | Failure Mode | Potential Risk | O | Resulting Influence | S | Detection Method | D | RPN |
---|---|---|---|---|---|---|---|---|
Human | data recording | misregistration | 2 | analysis result error | 4 | manual examination | 2 | 16 |
data processing | miscalculation | 2 | analysis result error | 4 | manual examination | 2 | 16 | |
instrument using | disoperation | 2 | analysis result error | 3 | instrument history | 2 | 12 | |
weigh | weighing error | 3 | influence in solvents, mobile phases, and percolations | 3 | visual check | 3 | 27 | |
solution preparation | solution formulation error | 2 | influence in solvents, mobile phases, and percolations | 3 | visual check | 5 | 30 | |
Instrument | pipette | error of scale | 2 | solution formulation error | 2 | visual check | 5 | 20 |
HPLC | instrument failure | 2 | unable to analyze | 5 | service | 2 | 20 | |
pH meter | instrument failure | 2 | influence in mobile phase pH | 4 | pH test paper | 4 | 32 | |
balance | instrument uncalibrated | 2 | weighing error | 3 | visual check | 3 | 18 | |
Milli-Q ultrapure water machine | fault filter | 1 | influences solution preparation | 2 | service | 4 | 8 | |
ultrasonic cleaning machine | instrument failure | 2 | influences solution preparation | 1 | visual check | 2 | 4 | |
centrifugal enrichment freeze-drying system | instrument failure | 2 | influences solution preparation | 5 | visual check | 2 | 20 | |
EP tube | error of scale | 2 | influences solution preparation and sample preparation | 1 | visual check | 4 | 8 | |
Material | TCM herbal slices | quality difference in herbal slices | 2 | difference in active ingredient content | 3 | HPLC | 3 | 18 |
acetonitrile | contaminated | 2 | influences mobile phase | 4 | HPLC | 4 | 32 | |
methanol | contaminated | 2 | influences mobile phase | 4 | HPLC | 4 | 32 | |
acetic acid | contaminated | 2 | influences mobile phase pH | 4 | HPLC | 4 | 32 | |
ammonium acetate | contaminated | 2 | influences mobile phase pH | 4 | HPLC | 4 | 32 | |
Sample | volume of redissolved solvent | unreasonable volume of redissolved solvent | 4 | low chromatographic peak response value | 4 | HPLC | 4 | 64 |
resoluble solvent | effect on sample dissolution | 4 | influences chromatographic peak response and peak shape | 4 | HPLC | 4 | 64 | |
sample bomb | contaminated/sample volatilization | 2 | influences chromatographic peak response | 3 | HPLC | 4 | 24 | |
centrifugal concentration temperature | if the temperature is too low, the preparation time is long, and if the temperature is too high, the components are volatilized. | 4 | influences chromatographic peak response | 4 | HPLC | 4 | 64 | |
HPLC mothod | chromatographic column | unsuitable for target component separation | 4 | influences component separation and analysis time | 5 | HPLC | 4 | 80 |
column temperature | unsuitable for target component separation | 4 | influences component separation and analysis time | 5 | HPLC | 4 | 80 | |
composition of the mobile phase system | unsuitable for target component separation | 4 | influences component separation and analysis time | 5 | HPLC | 4 | 80 | |
flow rate | unsuitable for target component separation | 4 | influences component separation and analysis time | 5 | HPLC | 4 | 80 | |
pH | unsuitable for target component separation | 4 | influences component separation and peak shape | 5 | HPLC | 4 | 80 | |
injection volume | unsuitable for target component separation | 3 | low chromatographic peak response | 4 | HPLC | 4 | 48 | |
detection wavelength | unsuitable for target component separation | 4 | low absorption and large interference | 5 | HPLC | 4 | 80 | |
volume ratio of mobile phase | unsuitable for target component separation | 4 | influences component separation and analysis time | 5 | HPLC | 5 | 80 | |
Environment | temperature | influence on column gentle sample | 3 | influences component separation and analysis time | 2 | thermometer | 2 | 12 |
humidity | effect on instruments, weighing, etc. | 3 | influences component separation and analysis time | 2 | thermometer | 2 | 12 | |
illumination | changes in the chemical composition of the reagent or side reactions occur | 2 | influences component separation and analysis time | 1 | HPLC | 4 | 8 | |
dust disturbance | effect on some precision instruments | 1 | influences component separation and analysis time | 1 | HPLC | 2 | 2 |
Run | Analytical Method Parameter | Chromatographic Response | |||||
---|---|---|---|---|---|---|---|
X1 (°C) | X2 | X3 (mL/min) | X4 (%) | Y1 | Y2 | Y3 (min) | |
1 | 35.0 | 4.50 | 0.200 | 88.0 | 1.68 | 0.0100 | 16.9 |
2 | 35.0 | 7.00 | 0.200 | 92.0 | 0.860 | 0.840 | 17.6 |
3 | 30.0 | 5.75 | 0.200 | 90.0 | 0.530 | 1.02 | 17.8 |
4 | 35.0 | 4.50 | 0.200 | 92.0 | 1.29 | 0.910 | 17.5 |
5 | 25.0 | 7.00 | 0.200 | 88.0 | 3.00 | 0.500 | 17.9 |
6 | 35.0 | 5.75 | 0.250 | 90.0 | 1.08 | 1.57 | 15.2 |
7 | 25.0 | 4.50 | 0.200 | 92.0 | 2.79 | 1.09 | 18.9 |
8 | 25.0 | 5.75 | 0.250 | 90.0 | 3.16 | 1.90 | 16.5 |
9 | 25.0 | 7.00 | 0.300 | 88.0 | 2.83 | 2.88 | 14.9 |
10 | 35.0 | 7.00 | 0.300 | 88.0 | 1.32 | 2.63 | 13.7 |
11 | 30.0 | 5.75 | 0.250 | 90.0 | 1.29 | 1.87 | 15.9 |
12 | 30.0 | 5.75 | 0.250 | 88.0 | 1.39 | 1.43 | 15.7 |
13 | 30.0 | 7.00 | 0.250 | 90.0 | 3.44 | 2.02 | 16.0 |
14 | 35.0 | 7.00 | 0.300 | 92.0 | 1.84 | 2.90 | 13.8 |
15 | 35.0 | 4.50 | 0.300 | 92.0 | 2.07 | 2.77 | 13.6 |
16 | 25.0 | 7.00 | 0.300 | 92.0 | 2.16 | 3.96 | 15.6 |
17 | 30.0 | 5.75 | 0.250 | 90.0 | 1.33 | 1.84 | 15.9 |
18 | 30.0 | 4.50 | 0.250 | 90.0 | 2.88 | 2.11 | 15.8 |
19 | 30.0 | 5.75 | 0.300 | 90.0 | 1.25 | 3.05 | 14.5 |
20 | 25.0 | 7.00 | 0.200 | 92.0 | 2.50 | 0.980 | 18.9 |
21 | 30.0 | 5.75 | 0.250 | 90.0 | 1.30 | 1.96 | 15.9 |
22 | 35.0 | 4.50 | 0.300 | 88.0 | 2.02 | 2.58 | 13.4 |
23 | 25.0 | 4.50 | 0.300 | 88.0 | 3.24 | 3.17 | 14.8 |
24 | 35.0 | 7.00 | 0.200 | 88.0 | 1.17 | 0.480 | 17.0 |
25 | 30.0 | 5.75 | 0.250 | 92.0 | 1.37 | 2.27 | 16.3 |
26 | 25.0 | 4.50 | 0.200 | 88.0 | 2.73 | 0.550 | 17.9 |
27 | 30.0 | 5.75 | 0.250 | 90.0 | 1.33 | 1.86 | 15.9 |
28 | 25.0 | 4.50 | 0.300 | 92.0 | 3.27 | 4.23 | 15.5 |
Y1 | Y2 | Y3 (min) | ||||
---|---|---|---|---|---|---|
Model Term | Coefficient | p Value | Coefficient | p Value | Coefficient | p Value |
Constant | 1.60 | 0 | 1.89 | 0 | 15.9 | 0 |
X1 | −0.729 | <0.0001 | −0.264 | <0.0001 | −0.674 | <0.0001 |
X2 | - | - | - | - | 0.0758 | <0.0001 |
X3 | 0.267 | 0.0043 | 1.22 | <0.0001 | −1.71 | <0.0001 |
X4 | - | - | 0.326 | <0.0001 | 0.296 | <0.0001 |
X12 | 0.475 | 0.0264 | −0.191 | 0.0064 | ||
X22 | 0.705 | 0.0015 | 0.221 | 0.0015 | - | - |
X32 | −0.562 | 0.0097 | - | - | 0.225 | <0.0001 |
X1X2 | - | - | 0.0622 | 0.0737 | - | - |
X1X3 | - | - | −0.170 | <0.0001 | −0.107 | <0.0001 |
X1X4 | - | - | −0.0983 | 0.0079 | −0.108 | <0.0001 |
X2X3 | - | - | - | - | 0.0330 | 0.0495 |
X3X4 | - | - | - | - | −0.0891 | <0.0001 |
R2 | 0.7754 | 0.9856 | 0.9979 | |||
Model p value | <0.0001 | <0.0001 | <0.0001 |
Collection Time (min) | Uridine (μg/mL) | Adenine (μg/mL) | 5-Hydroxymethylfurfural (μg/mL) | Guanosine (μg/mL) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Mean ± SD | The Lower Limit of the 95% Confidence Interval | The Upper Limit of the 95% Confidence Interval | Mean ± SD | The Lower Limit of the 95% Confidence Interval | The Upper Limit of the 95% Confidence Interval | Mean ± SD | The Lower Limit of the 95% Confidence Interval | The Upper Limit of the 95% Confidence Interval | Mean ± SD | The Lower Limit of the 95% Confidence Interval | The Upper Limit of the 95% Confidence Interval | |
10 | 26.8 ± 0.761 | 24.9 | 28.6 | 13.8 ± 0.185 | 13.3 | 14.3 | 21.3 ± 0.352 | 20.4 | 22.2 | 22.6 ± 0.642 | 21.0 | 24.2 |
20 | 31.4 ± 0.398 | 30.5 | 32.4 | 16.7 ± 0.170 | 16.3 | 17.1 | 24.9 ± 0.319 | 24.1 | 25.7 | 26.9 ± 0.964 | 24.5 | 29.3 |
30 | 32.1 ± 0.298 | 31.3 | 32.8 | 17.5 ± 0.0173 | 17.5 | 17.6 | 25.4 ± 0.0185 | 25.3 | 25.4 | 28.5 ± 0.564 | 27.1 | 29.9 |
50 | 27.9 ± 0.237 | 27.3 | 28.5 | 16.2 ± 0.185 | 15.8 | 16.7 | 21.6 ± 0.0555 | 21.4 | 21.7 | 25.3 ± 0.454 | 24.1 | 26.4 |
70 | 25.7 ± 0.635 | 24.1 | 27.3 | 15.1 ± 0.635 | 13.5 | 16.6 | 19.8 ± 0.0647 | 19.6 | 20.0 | 24.0 ± 0.285 | 23.3 | 24.8 |
100 | 21.5 ± 0.170 | 21.1 | 22.0 | 13.6 ± 0.0927 | 13.3 | 13.8 | 16.6 ± 0.0940 | 16.3 | 16.8 | 20.2 ± 0.377 | 19.3 | 21.1 |
130 | 19.5 ± 0.645 | 17.9 | 21.1 | 12.5 ± 0.170 | 12.0 | 12.9 | 15.7 ± 0.204 | 15.2 | 16.3 | 18.8 ± 0.282 | 18.1 | 19.5 |
160 | 18.6 ± 0.581 | 17.2 | 20.0 | 11.4 ± 0.0173 | 11.3 | 11.4 | 14.9 ± 0.138 | 14.5 | 15.2 | 17.5 ± 0.252 | 16.8 | 18.1 |
200 | 17.4 ± 0.102 | 17.1 | 17.6 | 10.1 ± 0.133 | 9.75 | 10.4 | 13.9 ± 0.0236 | 13.8 | 13.9 | 15.9 ± 0.152 | 15.5 | 16.2 |
250 | 14.8 ± 0.0657 | 14.6 | 14.9 | 8.55 ± 0.0378 | 8.45 | 8.64 | 12.2 ± 0.0415 | 12.1 | 12.3 | 13.6 ± 0.103 | 13.4 | 13.9 |
310 | 5.62 ± 0.180 | 5.17 | 6.06 | 4.49 ± 0.0351 | 4.41 | 4.58 | 3.80 ± 0.0558 | 3.66 | 3.94 | 6.39 ± 0.103 | 6.13 | 6.64 |
370 | 2.83 ± 0.0313 | 2.75 | 2.91 | 2.49 ± 0.0329 | 2.46 | 2.52 | 1.39 ± 0.0238 | 1.34 | 1.45 | 3.56 ± 0.0630 | 3.40 | 3.72 |
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Zhao, M.; Tai, Y.; Wu, G.; Ding, F.; Qu, H.; Gong, X. Integrated Application of Risk Management Techniques in Developing an Analysis Method for Traditional Chinese Medicine: A Case Study of a Percolation Solution for Xiaochaihu Capsules. Chemosensors 2024, 12, 161. https://doi.org/10.3390/chemosensors12080161
Zhao M, Tai Y, Wu G, Ding F, Qu H, Gong X. Integrated Application of Risk Management Techniques in Developing an Analysis Method for Traditional Chinese Medicine: A Case Study of a Percolation Solution for Xiaochaihu Capsules. Chemosensors. 2024; 12(8):161. https://doi.org/10.3390/chemosensors12080161
Chicago/Turabian StyleZhao, Mintong, Yanni Tai, Gelin Wu, Feng Ding, Haibin Qu, and Xingchu Gong. 2024. "Integrated Application of Risk Management Techniques in Developing an Analysis Method for Traditional Chinese Medicine: A Case Study of a Percolation Solution for Xiaochaihu Capsules" Chemosensors 12, no. 8: 161. https://doi.org/10.3390/chemosensors12080161