Evaluation of LC Methods for the Separation of Amoxicillin and Its Related Substances

Zhang, Yongxin; Roets, Eugène; Moreno, M. L.; Porqueras, E.; Hoogmartens, Jos

doi:10.1080/10826079608014013

Cited by 11 publications

(5 citation statements)

References 17 publications

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“…Uracil ( t 0 -marker), propiophenone, butyrophenone and benzophenone were purchased from Sigma-Aldrich (Steinheim, Germany). 2-hydroxy-3(4-hydroxy)phenylpyrazine (in short 3-PP-2-OL) is an impurity of the antibiotic amoxicillin [45] and was chosen as small pharmaceutical test compound (MW=188.18) to evaluate the column performance, because it eluted with a sufficiently high retention factor (similar to butyrophenone) at low acetonitrile (ACN) concentration (ACN ≥ 5% v). ACN Supra-Gradient grade was purchased from Biosolve (Valkenswaard, Netherlands).…”

Section: Methodsmentioning

confidence: 99%

Kinetic performance comparison of fully and superficially porous particles with sizes ranging between 2.7 μm and 5 μm: Intrinsic evaluation and application to a pharmaceutical test compound

Broeckhoven

Cabooter

Desmet

2013

Journal of Pharmaceutical Analysis

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The reintroduction of superficially porous particles has resulted in a leap forward for the separation performance in liquid chromatography. The underlying reasons for the higher efficiency of columns packed with these particles are discussed. The performance of the newly introduced 5 μm superficially porous particles is evaluated and compared to 2.7 μm superficially porous and 3.5 and 5 μm fully porous columns using typical test compounds (alkylphenones) and a relevant pharmaceutical compound (impurity of amoxicillin). The 5 μm superficially porous particles provide a superior kinetic performance compared to both the 3.5 and 5 μm fully porous particles over the entire relevant range of separation conditions. The performance of the superficially porous particles, however, appears to depend strongly on retention and analyte properties, emphasizing the importance of comparing different columns under realistic conditions (high enough k) and using the compound of interest.

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Section: Methodsmentioning

confidence: 99%

Kinetic performance comparison of fully and superficially porous particles with sizes ranging between 2.7 μm and 5 μm: Intrinsic evaluation and application to a pharmaceutical test compound

Broeckhoven

Cabooter

Desmet

2013

Journal of Pharmaceutical Analysis

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“…Many chromatographic methods were developed to separate AMCT from 4HPG. 7,9,[11][12][13] However, in industrial processes, chromatography is often not desirable due to its high cost. Repeated crystallization is often used to enhance the purity of the product but the yield can be sacrificed in the process.…”

Section: Papermentioning

confidence: 99%

Purification of amoxicillin trihydrate by impurity-coformer complexation in solution

et al. 2013

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In this work, we demonstrated the purification of amoxicillin trihydrate (AMCT) by the formation of 4-hydroxyphenylglycine (4HPG)-coformer complex in solution. Without advanced knowledge of cocrystal formation of 4HPG, a workflow was established to choose the optimal coformer and the amount of coformer to add for a specific target/impurity system. Forty-seven compounds were chosen and screened due to their functional groups having the potential to form heterosynthons with the functional groups on 4HPG. Using solid-state grinding, eleven compounds were selected as coformers for separation experiments because they can form cocrystals with 4HPG but not AMCT. Four compounds, 2-picolinic acid, L-lysine, L-leucine, and L-isoleucine were shown to enhance AMCT purity the most. The purities of the AMCT crystals crystallized from solutions with a 1 : 10 4HPG : AMCT ratio and with these four compounds were significantly greater than that without the addition of coformer and greater than that obtained from a second crystallization from fresh solvent. By varying the coformer-to-4HPG ratio, we can correlate the purification results to the level of complexation in the solution. In addition, the proposed separation method has practical uses and can be applied to expensive products where low yield is unacceptable.

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“…Several LC methods have been reported for assay of amoxicillin in drug substance [3][4][5] and for analysis of related substances in drug substance and drug products [4][5][6][7][8][9], dosage forms [10][11][12][13][14][15][16], and premixes [17,18]. Some LC methods with UV detection have been described for separation of sidechain diastereo isomers [19], C5 epimers of amoxicilloic acids [20,21], amoxicillin and amoxicillin dimer [22], and impurities eluted before amoxicillin [23].…”

Section: Introductionmentioning

confidence: 99%

“…Although an LC method with UV and mass spectrometric detection for related substances has also been reported [24], no validated stabilityindicating LC method has been reported for separation and quantitative determination of amoxicillin (a) and its related substances including isomers (2R)-2-amino-2-(4-hydroxyphenyl) acetic acid (b), amoxicilloic acids 1 and 2 (c and d), 6-aminopenicillanic acid (e), L-amoxicillin (f), amoxilloic acids 1 and 2 (g and i), (4-hydroxyphenyl)glycylamoxicillin (h), amoxicillin diketopiperazines 1 and 2 (j and k), (2R)-2-[(2,2-dimethylpropanoyl)amino]-2-(4-hydroxyphenyl) acetic acid (l), 3-(4-hydroxyphenyl)pyrazine-2-ol (m), amoxicilloic acid dimers 1 and 2 (n and o), amoxiamoxicilloic acid dimers 1 and 2 (p and r), 6-aminopenicillanic acid amoxicillin amide (q), and N-pivaloylamoxicillin (s). A gradient LC method [5] based on the USP method [4] has been proposed for purity control of related substances in amoxicillin drug substance; it was specified in the European Pharmacopoeia and further examined in a collaborative study. LC-UV and LC-MS methods have been reported for separation and identification of only thirteen of the potential impurities of amoxicillin [24].…”

Section: Introductionmentioning

confidence: 99%

“…LC-UV and LC-MS methods have been reported for separation and identification of only thirteen of the potential impurities of amoxicillin [24]. These methods [5,24] are neither validated nor stability indicating. This paper reports the development of an LC method for separation of individual related substances of amoxicillin and a newly identified impurity (Fig.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

RP-HPLC method for analysis of related substances in amoxicillin drug substance

Raju¹,

Sharma²,

Rao³

et al. 2009

Acta Chromatographica

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Linear gradient HPLC on a C 8 column has been used for separation of individual related substances of amoxicillin listed in the European Pharmacopoeia and a newly identified degradation impurity. The USP plate count for the amoxicillin peak was more than 3000 and USP tailing for the same peak was less than 2.0. Forced degradation studies were conducted on amoxicillin drug substance using ICH stress study guidelines to demonstrate the specificity and stability-indicating nature of the method. A new impurity observed after thermal and alkaline degradation was identified as N-pivaloylamoxicillin. The LOD and LOQ for individual related substances were below 0.045 and 0.086% (w/w), respectively. The method was fully validated in accordance with ICH analytical method validation guidelines. The results of the study prove the method is specific, precise, linear, robust, and can be used for evaluation of the stability of amoxicillin drug substance.

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Evaluation of LC Methods for the Separation of Amoxicillin and Its Related Substances

Cited by 11 publications

References 17 publications

Kinetic performance comparison of fully and superficially porous particles with sizes ranging between 2.7 μm and 5 μm: Intrinsic evaluation and application to a pharmaceutical test compound

Kinetic performance comparison of fully and superficially porous particles with sizes ranging between 2.7 μm and 5 μm: Intrinsic evaluation and application to a pharmaceutical test compound

Purification of amoxicillin trihydrate by impurity-coformer complexation in solution

RP-HPLC method for analysis of related substances in amoxicillin drug substance

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