Leveraging AQbD Principles for Development of Challenging Drug Substance Stability-Indicating Methods

2021 ◽  
Author(s):  
Elizabeth M. Yuill ◽  
Kevin M. Ileka ◽  
Thomas E. La Cruz ◽  
Jieming Li ◽  
Jonathan G. Shackman ◽  
...  
Keyword(s):  
Drug Substance ◽  
Stability Indicating

Development and Validation of Two Robust Stability-Indicating Chromatographic Methods for Determination of Metolazone in Drug Substance and Pharmaceutical Dosage Form in the Presence of Its Degradation Products and Characterization of Main Degradation Products Based on LC-MS

2019 ◽  
Vol 58 (3) ◽  
pp. 251-261
Author(s):  
Hala E Zaazaa ◽  
Rasha Abdel-Ghany ◽  
M Abdelkawy ◽  
Mahmoud Sayed
Keyword(s):  
Dosage Form ◽  
Degradation Products ◽  
Hplc Method ◽  
Drug Substance ◽  
Design Parameters ◽  
Pharmaceutical Dosage Form ◽  
Stability Indicating ◽  
Chromatographic Methods ◽  
Hptlc Method

Abstract Two robust and selective stability-indicating chromatographic methods were developed and validated for the determination of metolazone in drug substance and pharmaceutical dosage form in the presence of its degradation products. The HPLC method employed a Kromasil C18 (250 × 4.6,5 μm) column and a mobile phase of acetonitrile: 0.2% orthophosphoric acid (32:68 v/v) at a flow rate 2 mL/min and detection at 238 nm. The separation was performed in HPLC isocratic mode. The robustness of the suggested method was assessed using the Plackett–Burman design, parameters affecting system suitability were established and non-significant intervals for the significant parameters were considered. The HPTLC method employed Nano-SIL-20 UV254 HPTLC plates as adsorbent, ethyl acetate: toluene: acetic acid solution (4:4:0.5, v/v/v), as a developing solvent system and densitometric detection at 238 nm. Metolazone was exposed to different stress conditions, including acid and alkaline hydrolysis and oxidative and photolytic degradation. The main degradation products obtained have been characterized and interpreted based on LC-MS. The linearity of the suggested methods was proved in the concentration range of 20–75 μg/mL for the HPLC method and 100–900 ng/spot for the HPTLC method. The suggested methods were validated according to international conference on harmonization guidelines. These methods were successfully dedicated for the estimation of metolazone in drug substance and pharmaceutical dosage form in the presence of its degradation products. The results of the suggested methods were evaluated and compared statistically with results obtained by an official method without finding any significant difference.

scholarly journals Development and validation of stability-indicating RP-HPLC method for determination of Olmesartan medoxomile in pharmaceutical dosage form and identification, characterization of alkaline degradation impurity of Olmesartan medoxomile drug substance as well as drug product

2012 ◽  
Vol 18 (4-1) ◽  
pp. 595-604 ◽  
Author(s):  
P.S. Jain ◽  
A.J. Chaudhari ◽  
S.J. Surana
Keyword(s):  
Degradation Product ◽  
Drug Product ◽  
Olmesartan Medoxomil ◽  
Hplc Method ◽  
Drug Substance ◽  
Alkaline Degradation ◽  
Stability Indicating ◽  
Rp Hplc

Olmesartan Medoxomil (OLME) belongs to a group of angiotensin II receptor blockers used as an antihypertensive agent and is currently being used for prevention of Hypertension. This paper describes the Validation and development of stability indicating RP-HPLC method for the determination of OLME in the presence of its degradation products generated from forced degradation study and characterization of degradation product (impurity). The assay involved gradient elution of OLME on An LC GC BDS C18 column (250 ? 4.5mm, 5-?m particle size) was employed for loading the sample. The mobile phase A consists of 7 ml Triethylamine in 1000 ml water (pH adjusted to 3.0 with orthophosphoric acid) and B contains acetonitrile. Quantification was achieved with photodiode array detection at 257 nm. The chromatographic separation was obtained with a retention time of 6.72 min, and the method was linear in the range 50-150 ?g/ml. The method was validated according to the ICH guidelines with respect to linearity, precision, accuracy, limit of detection (LOD), limit of quantification (LOQ), specificity and robustness. Impurity found in stressed and stability studies of Olmesartan Medoxomil in both drug substance and drug product are described. This degradation product is identified as 1-(biphenyl-4-ylmethyl)-1H-imidazole-5-carboxylic acid. An Alkaline degradation pathway of Olmesartan medoxomil, for the formation of this degradation product, has been proposed and degradation product was characterized.

Stability indicating ion chromatography method for the simultaneous determination of ibandronate sodium drug substance and its impurities

2011 ◽  
Vol 54 (3) ◽  
pp. 596-601 ◽  
Author(s):  
M. Narendra Kumar ◽  
K.S.R. Pavan Kumar ◽  
Vundavilli Jagadeesh Kumar ◽  
S. John Prasanna ◽  
Hemant Kumar Sharma ◽  
...  
Keyword(s):  
Simultaneous Determination ◽  
Ion Chromatography ◽  
Drug Substance ◽  
Chromatography Method ◽  
Stability Indicating
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