Practical and regulatory considerations for stability-indicating methods for the assay of bulk drugs and drug formulations

Maggio, Rubén M.; Vignaduzzo, Silvana E.; Kaufman, Teodoro S.

doi:10.1016/j.trac.2013.05.008

Cited by 61 publications

(33 citation statements)

References 120 publications

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“…Organized research into the methods for the analysis of impurities and degradation products is of significant importance due to the stringent requirements on control of quality of drug products. Comprehensive details on the degradation behaviour of drugs could help to maintain its quality and pharmaceutical safety …”

Section: Introductionmentioning

confidence: 99%

Characterization of degradation products of Ivabradine by LC‐HR‐MS/MS: a typical case of exhibition of different degradation behaviour in HCl and H₂SO₄ acid hydrolysis

et al. 2015

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A validated stability-indicating HPLC method was established, and comprehensive stress testing of ivabradine, a cardiotonic drug, was carried out as per ICH guidelines. Ivabradine was subjected to acidic, basic and neutral hydrolysis, oxidation, photolysis and thermal stress conditions, and the resulting degradation products were investigated by LC-PDA and LC-HR-MS/MS. The drug was found to degrade in acid and base hydrolysis. An efficient and selective stability assay method was developed on Phenomenex Luna C18 (250 × 4.6 mm, 5.0 µm) column using ammonium formate (10 mM, pH 3.0) and acetonitrile as mobile phase at 30 °C in gradient elution mode. The flow rate was 0.7 ml/min and detection wavelength was 286 nm. A total of five degradation products (I-1 to I-5) were identified and characterized by LC-HR-MS/MS in combination with accurate mass measurements. The drug exhibited different degradation behaviour in HCl and H2SO4 hydrolysis conditions. It is a unique example where two of the five degradation products in HCl hydrolysis were absent in H2SO4 acid hydrolysis. The present study provides guidance to revise the stress test for the determination of inherent stability of drugs containing lactam moiety under hydrolytic conditions. Most probable mechanisms for the formation of degradation products have been proposed on the basis of a comparison of the fragmentation pattern of the drug and its degradation products. In silico toxicity revealed that the degradation products (I-2 to I-5) were found to be severe irritants in case of ocular irritancy. The analytical assay method was validated with respect to specificity, linearity, range, precision, accuracy and robustness.

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Section: Introductionmentioning

confidence: 99%

Characterization of degradation products of Ivabradine by LC‐HR‐MS/MS: a typical case of exhibition of different degradation behaviour in HCl and H₂SO₄ acid hydrolysis

et al. 2015

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“…Various approaches are possible when evaluating method specificity [5][6][7][8]. Ideal demonstration of specificity for an HPTLC analytical procedure requires chromatographing simultaneously three types of samples: sample type 1 is the pure analyte or its reference standard, sample type 2 is the analyte mixed with a representative blank and all likely impurities, and sample type 3 is the representative blank mixed with all likely impurities.…”

Section: Specificitymentioning

confidence: 99%

Method Validation Approaches for Pharmaceutical Assessments – Highlights with High Performance Thin Layer Chromatographic (HPTLC) Techniques

Jenkins¹,

Diallo²,

Bethea³

et al. 2018

Calibration and Validation of Analytical Methods - A Sampling of Current Approaches

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Method validation is an important activity for pharmaceutical evaluations to ensure that analytical methods are suitable for their intended use. With particular focus on active ingredient and impurities, the implementation of different categories of method validation are explained for qualitative and quantitative methods. Detailed explanations with example approaches are provided for the key aspects of method validation, namely specificity, accuracy, linearity, limits of detection/quantitation, precision, robustness, and method range. While all of the sections outlined for method validation are generally applicable for a variety of techniques commonly used in pharmaceutical analysis (i.e., UV and HPLC instrumentation), focused attention is provided for examples that have been implemented using high performance thin layer chromatographic techniques.

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“…Stress testing should also include testing of the sensitivity of the drug substance to light. In addition to the above points, it is important to note that, with this information, the stability-indicating nature of the assay method can be checked [38].…”

Section: Identification Of Degradants In Drugs and Drug Productsmentioning

confidence: 99%

Identification in drug quality control and drug research

Gǒrög

2015

TrAC Trends in Analytical Chemistry

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Practical and regulatory considerations for stability-indicating methods for the assay of bulk drugs and drug formulations

Cited by 61 publications

References 120 publications

Characterization of degradation products of Ivabradine by LC‐HR‐MS/MS: a typical case of exhibition of different degradation behaviour in HCl and H₂SO₄ acid hydrolysis

Characterization of degradation products of Ivabradine by LC‐HR‐MS/MS: a typical case of exhibition of different degradation behaviour in HCl and H₂SO₄ acid hydrolysis

Method Validation Approaches for Pharmaceutical Assessments – Highlights with High Performance Thin Layer Chromatographic (HPTLC) Techniques

Identification in drug quality control and drug research

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Practical and regulatory considerations for stability-indicating methods for the assay of bulk drugs and drug formulations

Cited by 61 publications

References 120 publications

Characterization of degradation products of Ivabradine by LC‐HR‐MS/MS: a typical case of exhibition of different degradation behaviour in HCl and H2SO4 acid hydrolysis

Characterization of degradation products of Ivabradine by LC‐HR‐MS/MS: a typical case of exhibition of different degradation behaviour in HCl and H2SO4 acid hydrolysis

Method Validation Approaches for Pharmaceutical Assessments – Highlights with High Performance Thin Layer Chromatographic (HPTLC) Techniques

Identification in drug quality control and drug research

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Characterization of degradation products of Ivabradine by LC‐HR‐MS/MS: a typical case of exhibition of different degradation behaviour in HCl and H₂SO₄ acid hydrolysis

Characterization of degradation products of Ivabradine by LC‐HR‐MS/MS: a typical case of exhibition of different degradation behaviour in HCl and H₂SO₄ acid hydrolysis