Long‐term stability study of L‐adrenaline injections: Kinetics of sulfonation and racemization pathways of drug degradation

Stepensky, David; Chorny, Michael; Dabour, Ziad; Schumacher, Ilana

doi:10.1002/jps.20010

Cited by 31 publications

(31 citation statements)

References 6 publications

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“…L-adrenaline in the solution is subject to degradation during long-term storage, caused by oxidation, sulfonation, and racemization. Products of these reactions, including D-adrenaline and adrenaline sulfonate, do not have pharmacological activity comparable to L-adrenaline [41]. Therefore, the test results c test of L-adrenaline concentration in the stored product (relative to the labeled amount) were compared with the lower specification limit c l.s.l = 90.0 %.…”

Section: Example 3 Oos Test Results In Long-term Stability Study Of mentioning

confidence: 99%

IUPAC/CITAC Guide: Investigating out-of-specification test results of chemical composition based on metrological concepts (IUPAC Technical Report)

Kuselman

Pennecchi

Burns

et al. 2012

Pure and Applied Chemistry

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A metrological background for investigating out-of-specification (OOS) test results of chemical composition is discussed. When an OOS test result is identified, it is important to determine its root causes and to avoid reoccurrence of such results. An investigation of the causes based on metrological concepts is proposed. It includes assessment of validation data of the measurement process and its metrological traceability chains, evaluation of measurement uncertainty, and related producer's and consumer's risks. This approach allows distinguishing between OOS test results that indicate an actual change in chemical composition of an analyzed object, and OOS test results that are metrologically related with a certain confidence probability, i.e., caused by measurement problems, while the analyzed object still meets the specification requirements at the time of testing.Practical examples illustrating applications of the described approach in environ mental and food analysis, as well in drug analysis and stability study of drug products, are described. Acceptance limits, warning and action lines for the test results, and corresponding producer's and consumer's risks are discussed.

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Section: Example 3 Oos Test Results In Long-term Stability Study Of mentioning

confidence: 99%

IUPAC/CITAC Guide: Investigating out-of-specification test results of chemical composition based on metrological concepts (IUPAC Technical Report)

Kuselman

Pennecchi

Burns

et al. 2012

Pure and Applied Chemistry

View full text Add to dashboard Cite

show abstract

“…If the number of degradant peaks is the same in both separations, and if the are percent of the main component is the same in both separations, then there can be reasonable confidenc that all the degradants have been resolved from the main component. Automated versions of this approach have been successfully utilized in a multidimensional screening with instrumentation capable of systematically evaluating several different columns and eluents for impurity analysis [27][28][29] .…”

Section: Figure 1: Normalised Signals For Pure and Impure Peakmentioning

confidence: 99%

Untitled

2012

IJPSR

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High performance liquid chromatography is one of the most accurate methods widely used for the quantitative as well as qualitative analysis of drug product and is used for determining drug product stability. Stability indicating HPLC methods are used to separate various drug related impurities that are formed during the synthesis or manufacture of drug product. This article discusses the strategies and issues regarding the development of stability indicating HPLC system for drug substance. A number of key chromatographic factors were evaluated in order to optimize the detection of all potentially relevant degradants. The method should be carefully examined for its ability to distinguish the primary drug components from the impurities. New chemical entities and drug products must undergo forced degradation studies which would be helpful in developing and demonstrating the specificity of such stability indicating methods. At every stage of drug development practical recommendations are provided which will help to avoid failures. INTRODUCTION:Most of the optimization of HPLC method development have been focused on the optimization of HPLC conditions. This article will look at this topic from other perspectives. Forced degradation or stress testing is undertaken to demonstrate specificity when developing stability-indicating methods, particularly when little information is available about potential degradation products. These studies also provide information about the degradation pathways and degradation products that could form during storage.

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“…According to ICH guidelines, the content of D-forms must not be higher than from 0.1 to 1.0%, depending on the amount of drug substance administered per day (http://www.ich.org/cache/compo/ 276-2541.html, checked on December 2008) [13]. Moreover, L-enantiomers in solution can be partially or completely racemized during long storage [14,15]. As a result, it is important to know the enantiomeric purity of EP or NEP in pharmaceutical formulations for adequate usage, being the optical rotation method often adopted for this purpose, although it is sometimes not applicable on account of low sensitivity [10].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous separation of epinephrine and norepinephrine enantiomers by EKC: Application to the analysis of pharmaceutical formulations

et al. 2009

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A new analytical methodology using EKC with a CD as chiral selector was developed enabling the simultaneous enantiomeric separation of two chiral neurotransmitters (epinephrine and norepinephrine). Different experimental conditions (type and\ud concentration of the chiral selector, nature and concentration of buffer and separation voltage) were optimized. The use of 10mM carboxyethyl-b-CD in 100mM Tris-phosphate buffer (pH 5.0) with an applied voltage of 30 kV and a temperature of 151C allowed\ud the separation of epinephrine and norepinephrine enantiomers with high chiral resolution (Rs42.5). Moreover, after evaluating the analytical characteristics of the method, it was applied to the quantitation and purity testing of L-epinephrine as active pharmaceutical ingredient in pharmaceutical formulations where D-epinephrine and L/D-norepinephrine can be present as impurities

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Long‐term stability study of L‐adrenaline injections: Kinetics of sulfonation and racemization pathways of drug degradation

Cited by 31 publications

References 6 publications

IUPAC/CITAC Guide: Investigating out-of-specification test results of chemical composition based on metrological concepts (IUPAC Technical Report)

IUPAC/CITAC Guide: Investigating out-of-specification test results of chemical composition based on metrological concepts (IUPAC Technical Report)

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Simultaneous separation of epinephrine and norepinephrine enantiomers by EKC: Application to the analysis of pharmaceutical formulations

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