Analytical Quality By Design Methodology For Botanical Raw Material Analysis: A Case Study of Flavonoids in Genkwa Flos

AbstractThe present study introduces a systematic approach using analytical quality by design (AQbD) methodology for the development of a qualified liquid chromatographic analytical method, which is a challenge in herbal medicinal products due to the intrinsic complex components of botanical sources. The ultra-high-performance liquid chromatography-photodiode array-mass spectrometry (UHPLC-PDA-MS) technique for 11 flavonoids in Genkwa Flos was utilized through the entire analytical processes, from the risk assessment study to the factor screening test, and finally in method optimization employing central composite design (CCD). In this approach, column temperature and mobile solvent slope were found to be critical method parameters (CMPs) and each of the eleven flavonoid peaks’ resolution values were used as critical method attributes (CMAs) through data mining conversion formulas. An optimum chromatographic method in the design space was calculated by mathematical and response surface methodology (RSM). The established chromatographic condition is as follows: acetonitrile and 0.1% formic acid gradient elution (0–13 min, 10–45%; 13–13.5 min, 45–100%; 13.5–14 min, 100–10%; 14–15 min, 10% acetonitrile), column temperature 28℃, detection wavelength 335 nm, and flow rate 0.35 mL/min using C18 (50 × 2.1 mm, 1.7 μm) column. A validation study was also performed successfully for apigenin 7-O-glucuronide, apigenin, and genkwanin. A few important validation results were as follows: linearity over 0.999 coefficient of correlation, detection limit of 2.87–22.41, quantitation limit of 8.70–67.92, relative standard deviation of precision less than 0.22%, and accuracy between 100.13 and 102.49% for apigenin, genkwanin, and apigenin 7-O-glucuronide. In conclusion, the present design-based approach provide a systematic platform that can be effectively applied to ensure pharmaceutically qualified analytical data from complex natural products based botanical drug.

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Developing an Improved UHPLC Method for Efficient Determination of European Pharmacopeia Process-Related Impurities in Ropinirole Hydrochloride Using Analytical Quality by Design Principles

Molecules ◽

10.3390/molecules25112691 ◽

2020 ◽

Vol 25 (11) ◽

pp. 2691

Author(s):

Tim Tome ◽

Aleš Obreza ◽

Zdenko Časar

Keyword(s):

High Performance ◽

Quality By Design ◽

High Performance Liquid Chromatographic ◽

Reversed Phase ◽

Fractional Factorial ◽

Linear Regression Method ◽

Analytical Quality ◽

Column Temperature ◽

Related Impurities ◽

Ropinirole Hydrochloride

This article presents the development of a reversed-phase ultra-high-performance liquid chromatographic method for determining process-related impurities in ropinirole hydrochloride drug substance applying the analytical quality by design approach. The current pharmacopeial method suffers from selectivity issues due to two coelutions of two pairs of impurities. The development of a new method began with preliminary experiments, based on which the Acquity UPLC BEH C8 was selected as the most appropriate column. The effects of six different critical method parameters (CMPs) were then investigated using a fractional factorial screening design. Column temperature, the ratio of methanol in mobile phase B, and gradient slope turned out to be highly significant CMPs in achieving critical resolutions, and they were further evaluated using a central composite face-centered response-surface design. Mathematical models were created by applying a multiple linear regression method. Based on the elution order of an unknown degradation impurity and impurity C, two design spaces were established, and for each design space an optimal combination of CMPs was determined. The method developed was validated for precision, accuracy, linearity, and sensitivity, and it was proven suitable for determining nine process-related impurities of ropinirole.

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Analytical quality by design for liquid chromatographic method development

Handbook of Analytical Quality by Design ◽

10.1016/b978-0-12-820332-3.00010-8 ◽

2021 ◽

pp. 87-97

Author(s):

Sarwar Beg ◽

Mahfoozur Rahman

Keyword(s):

Chromatographic Method ◽

Method Development ◽

Quality By Design ◽

Analytical Quality ◽

Liquid Chromatographic Method ◽

Liquid Chromatographic

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Development of a New High-Performance Liquid Chromatographic Method for the Determination of Ceftazidime

Journal of AOAC International ◽

10.1093/jaoac/91.4.739 ◽

2008 ◽

Vol 91 (4) ◽

pp. 739-743 ◽

Cited By ~ 11

Author(s):

Andréia de Haro Moreno ◽

Hérida Regina Nunes Salgado

Keyword(s):

High Performance ◽

High Performance Liquid Chromatographic ◽

Reversed Phase ◽

Hplc Method ◽

Calibration Graph ◽

Raw Material ◽

Relative Standard ◽

Validation Parameters ◽

Liquid Chromatographic

Abstract A rapid, accurate, and sensitive high-performance liquid chromatographic (HPLC) method was developed and validated for the determination of ceftazidime in pharmaceuticals. The method validation parameters yielded good results and included range, linearity, precision, accuracy, specificity, and recovery. The excipients in the commercial powder for injection did not interfere with the assay. Reversed-phase chromatography was used for the HPLC separation on a Waters C18 (WAT 054275; Milford, MA) column with methanolwater (70 + 30, v/v) as the mobile phase pumped isocratically at a flow rate of 1.0 mL/min. The effluent was monitored at 245 nm. The calibration graph for ceftazidime was linear from 50.0 to 300.0 g/mL. The values for interday and intraday precision (relative standard deviation) were <1. The results obtained by the HPLC method were calculated statistically by analysis of variance. We concluded that the HPLC method is satisfactory for the determination of ceftazidime in the raw material and pharmaceuticals.

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High-Performance Liquid Chromatographic Fingerprint for Quality Control of Terminalia arjuna Containing Ayurvedic churna Formulation

Journal of AOAC International ◽

10.1093/jaoac/92.4.1016 ◽

2009 ◽

Vol 92 (4) ◽

pp. 1016-1020 ◽

Cited By ~ 10

Author(s):

Sohan S Chitlange ◽

Prajakta S Kulkarni ◽

Dada Patil ◽

Bhushan Patwardhan ◽

Rabindra K Nanda

Keyword(s):

Quality Control ◽

High Performance ◽

Raw Materials ◽

High Performance Liquid Chromatographic ◽

Raw Material ◽

Terminalia Arjuna ◽

Hplc Fingerprint ◽

Ayurvedic Drugs ◽

Quality Control Tool ◽

Liquid Chromatographic

Abstract Because Ayurvedic herbal preparations contain a myriad of compounds in complex matrixes, it is difficult to establish quality control standards for raw materials and to standardize finished Ayurvedic drugs. A novel, accurate, and valid fingerprint method was developed using HPLC for quality control of a traditional Ayurvedic Arjuna churna formulation, which is used as a cardiotonic drug. Comprehensive comparison of chromatograms of standardized formulation of Arjuna churna and marketed formulations revealed eight characteristic peaks in chromatograms, which unambiguously confirmed the presence of authentic raw material used in the formulation on the basis of their retention time values and UV data. An HPLC fingerprint was also developed for total sapogenins present in Terminalia arjuna. The six common peaks observed in chromatograms of isolated sapogenins, standardized formulations, and marketed formulations can serve as a quality control tool for qualitative estimation of total saponin glycosides present in an Arjuna churna formulation.

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Development and Validation of a Micellar High-Performance Liquid Chromatographic Method for Determination of Risedronate in Raw Material and in a Pharmaceutical Formulation: Application to Stability Studies

Journal of AOAC International ◽

10.1093/jaoac/93.4.1228 ◽

2010 ◽

Vol 93 (4) ◽

pp. 1228-1235 ◽

Cited By ~ 6

Author(s):

Mohamed Walash ◽

Mohamed Metwally ◽

Manal Eid ◽

Rania El-Shaheny

Keyword(s):

Mobile Phase ◽

High Performance ◽

Sodium Dodecyl ◽

Oxidative Degradation ◽

High Performance Liquid Chromatographic ◽

Hplc Method ◽

Raw Material ◽

Forced Degradation ◽

The Stability ◽

Liquid Chromatographic

Abstract A micellar HPLC method was developed for analysis of the antiosteoporosis drug risedronate. The analysis was carried out using a 250 4.6 mm id, 5 m particle size C18 Waters Symmetry column. The mobile phase consisted of 0.02 M sodium dodecyl sulfate + 0.3 triethylamine + 10 n-propanol, prepared in 0.02 M orthophosphoric acid. The pH of the mobile phase was adjusted to pH 6.0, and it was pumped at a flow rate of 0.7 mL/min with UV detection at 262 nm. The method showed good linearity in the range of 280 g/mL, with an LOD of 0.40 g/mL (1.31 106 M) and an LOQ of 1.21 g/mL. The suggested method was successfully applied for the analysis of risedronate in raw material and a tablet formulation, with average recoveries of 99.91 1.30 and 101.52 0.30, respectively. The stability-indicating capability of the proposed method was proved using forced degradation. By changing the pH of the mobile phase to 4.0, the oxidative degradation product could be separated from risedronate.

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Liquid-chromatographic analysis for methylphenidate (Ritalin) in serum.

Clinical Chemistry ◽

10.1093/clinchem/25.3.401 ◽

1979 ◽

Vol 25 (3) ◽

pp. 401-404 ◽

Cited By ~ 16

Author(s):

S J Soldin ◽

Y P Chan ◽

B M Hill ◽

J M Swanson

Keyword(s):

Chromatographic Analysis ◽

High Performance ◽

Plasma Sample ◽

Potassium Phosphate ◽

Internal Standard ◽

High Performance Liquid Chromatographic ◽

Column Temperature ◽

Liquid Chromatographic Method ◽

Liquid Chromatographic Analysis ◽

Liquid Chromatographic

Abstract We describe a "high performance" liquid chromatographic method for quantitating methylphenidate in serum. The internal standard, 4,5-diphenylimidazole, and serum or plasma sample are extracted in chloroform, evaporated, and redissolved in 20 mmol/L potassium phosphate (pH 3.5)/high-purity acetonitrile, 80/20 by vol. A centrifuged aliquot is chromatographed on mu-Bondapak C-18 with the phosphate/acetonitrile solvent as mobile phase, a flow rate of 1.6 mL/min, and a column temperature of 40 degrees C. Absorbances are read at 192 nm. This method reliably measures concentrations greater than 20 micrograms/L and has analytical recoveries of 74%.

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A Liquid-Chromatographic Analysis for Indomethacin in Serum

Clinical Chemistry ◽

10.1093/clinchem/25.4.589 ◽

1979 ◽

Vol 25 (4) ◽

pp. 589-591 ◽

Cited By ~ 7

Author(s):

Steven J Soldin ◽

Terese Gero

Keyword(s):

High Performance ◽

Potassium Phosphate ◽

Internal Standard ◽

Ethylene Dichloride ◽

Buffer System ◽

Potassium Phosphate Buffer ◽

Column Temperature ◽

Analytical Recovery ◽

Liquid Chromatographic Analysis ◽

Liquid Chromatographic

Abstract We describe a "high-performance" liquid-chromato-graphic assay for measuring indomethacin in 100 µL of serum. The procedure involves an ethylene dichloride extraction of indomethacin and internal standard (2,5-diphenyloxazole) from serum. The organic phase is separated and evaporated, and the residue dissolved in a 40/60 (by vol) mixture of potassium phosphate buffer (10 mmol/L, pH 3.0) and acetonitrile. An aliquot of this solution is injected into the chromatograph. We used a µ-Bondapak C-18 column with the above-mentioned buffer system as mobile phase, a flow rate of 3.0 mL/min, and a column temperature of 40 °C. Indomethacin and the internal standard are detected by their absorbance at 200 nm and quantitated by measuring peak heights. The procedure allows for the reliable analysis for indomethacin in serum at concentrations > 100 µg/L. Analytical recovery for indomethacin was 66-68%, and the method affords good day-to-day precision (CV <11 %).

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