Microbiological assay for the determination of meropenem in pharmaceutical dosage form

Mendez, Andreas Sebastian Loureiro; Weisheimer, Vanessa; Oppe, Tércio Paschke; Steppe, Martin; Schapoval, Elfrides E.S.

doi:10.1016/j.jpba.2004.11.030

Cited by 33 publications

(26 citation statements)

References 12 publications

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“…The microbiological assay described above was applied to determine the residual concentrations and potency of the API of meropenem products exposed to the mDHP extract (31). Standard curves of each meropenem product (freshly prepared duplicates ranging from 8 to 1,000 mg/liter) were used for references and plated simultaneously with the duplicate samples exposed to mDHP extract.…”

Section: Neutropenic Guinea Pig Soleus Infection Model (Sepsis)mentioning

confidence: 99%

Even Apparently Insignificant Chemical Deviations among Bioequivalent Generic Antibiotics Can Lead to Therapeutic Nonequivalence: the Case of Meropenem

Agudelo

Rodríguez

Peláez

et al. 2014

Antimicrob Agents Chemother

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e Several studies with animal models have demonstrated that bioequivalence of generic products of antibiotics like vancomycin, as currently defined, do not guarantee therapeutic equivalence. However, the amounts and characteristics of impurities and degradation products in these formulations do not violate the requirements of the U.S. Pharmacopeia (USP). Here, we provide experimental data with three generic products of meropenem that help in understanding how these apparently insignificant chemical differences affect the in vivo efficacy. Meropenem generics were compared with the innovator in vitro by microbiological assay, susceptibility testing, and liquid chromatography/mass spectrometry (LC/MS) analysis and in vivo with the neutropenic guinea pig soleus infection model (Pseudomonas aeruginosa) and the neutropenic mouse thigh (P. aeruginosa), brain (P. aeruginosa), and lung (Klebisella pneumoniae) infection models, adding the dihydropeptidase I (DHP-I) inhibitor cilastatin in different proportions to the carbapenem. We found that the concentration and potency of the active pharmaceutical ingredient, in vitro susceptibility testing, and mouse pharmacokinetics were identical for all products; however, two generics differed significantly from the innovator in the guinea pig and mouse models, while the third generic was therapeutically equivalent under all conditions. Trisodium adducts in a bioequivalent generic made it more susceptible to DHP-I hydrolysis and less stable at room temperature, explaining its therapeutic nonequivalence. We conclude that the therapeutic nonequivalence of generic products of meropenem is due to greater susceptibility to DHP-I hydrolysis. These failing generics are compliant with USP requirements and would remain undetectable under current regulations.

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Section: Neutropenic Guinea Pig Soleus Infection Model (Sepsis)mentioning

confidence: 99%

Even Apparently Insignificant Chemical Deviations among Bioequivalent Generic Antibiotics Can Lead to Therapeutic Nonequivalence: the Case of Meropenem

Agudelo

Rodríguez

Peláez

et al. 2014

Antimicrob Agents Chemother

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“…Literature survey reveals several analytical methods reported for the quantitative estimation of meropenem in pharmaceutical dosage form, including high-performance liquid chromatography (HPLC) [5][6][7], ultraviolet spectrophotometry [6] and microbiological assay [8]. The quantitation of meropenem in the presence of its degradation products has been studied.…”

Section: Introductionmentioning

confidence: 99%

Stability and degradation kinetics of meropenem in powder for injection and reconstituted sample

Mendez

Dalomo

Steppe

et al. 2006

Journal of Pharmaceutical and Biomedical Analysis

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“…Moreover, the development and validation of analytical methods to determine potency, such as microbiological assays, have recently received considerable attention, mainly from regulatory agencies, because of their importance in pharmaceutical analysis (Mendez et al, 2005;Moreno, Salgado, 2007;Salgado, Tozo, 2007;Lopes, Salgado, 2010;Cazedey, Salgado, 2011). Microbiological assays have the potential to prevent the possible loss of activity, while physicochemical methods do not prevent the loss of the antimicrobial potency (USP, 2008).…”

Section: Resultsmentioning

confidence: 99%

“…However, in the literature, there are a large number of reports describing the use of microbiological assays to assess the potency of many antibiotics (Marona, Schapoval, 1998;Mendez et al, 2005;Gomes, Salgado, 2006;Salgado, Lopes, Lucchesi, 2006;Vaugher, Breier, Schapoval, 2006;Souza et al, 2007;Moreno, Salgado, 2007;Salgado, Tozo, 2007;Schmidt et al, 2008;Lopes, Salgado, 2010;Cazedey, Salgado, 2011;Paim et al, 2011;Solano et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a microbiological assay for determination of chlorhexidine digluconate in aqueous solution

Fiorentino

Corrêa

Salgado

2013

Braz. J. Pharm. Sci.

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Chlorhexidine (CHX) is a broad-spectrum antiseptic that is used in many topical pharmaceutical formulations. Because there is no official microbiological assay reported in the literature that is used to quantify CHX, this paper reports the development and validation of a simple, sensitive, accurate and reproducible agar diffusion method for the dosage of chlorhexidine digluconate (CHX-D) in an aqueous solution. The assay is based on the inhibitory effect of CHX-D upon the strain of Staphylococcus aureus ATCC 25923, which is used as the test microorganism. The design 3x3 parallel-line model was used. The results were treated statistically by analysis of variance (ANOVA), and they were excellent in terms of linearity (r = 0.9999), presenting a significant regression between the zone diameter of growth inhibition and the logarithm of the concentration within the range of 0.5 to 4.5%. The results obtained were precise, having relative standard deviations (RSD) for intra-day and inter-day precision of 2.03% and 2.94%, respectively. The accuracy was 99.03%. The method proved to be very useful and appropriate for the microbiological dosage of CHX-D in pharmaceutical formulations; it might also be used for routine drug analysis during quality control in pharmaceutical industries.Uniterms: Agar diffusion. Antiseptic. Chlorhexidine. Microbiological assay. Quality control. Validation.Clorexidina (CHX) é um antisséptico com amplo espectro de ação utilizada em muitos tipos de preparações farmacêuticas para uso tópico. Uma vez que não há na literatura ensaio microbiológico oficial para quantificar a clorexidina, este trabalho objetivou o desenvolvimento e validação de um ensaio microbiológico simples, sensível, exato e reprodutível, por difusão em ágar, para doseamento de digliconato de clorexidina (CHX-D) em solução aquosa. O ensaio é baseado no efeito da inibição de Staphylococcus aureus ATCC 25923, utilizado como microorganismo teste, pela CHX-D. Utilizouse o delineamento 3x3. Os resultados foram verificados estatisticamente pela análise de variância (ANOVA) e apresentaram excelente linearidade (r = 0,9999), demonstrando que o método segue o modelo linear com regressão significativa entre o diâmetro da zona de inibição e o lagaritmo da concentração no intervalo de 0,5 a 4,5%. Os resultados obtidos foram precisos apresentando desvio padrão relativo (DPR) para precisão intra-dia de 2,03% e DPR para precisão inter-dias de 2,94%. A exatidão foi 99,03%. O método provou ser muito útil e apropriado para doseamento microbiológico da CHX-D em formas farmacêuticas e pode ser empregado para análise desta substância no controle de qualidade em indústrias farmacêuticas.Unitermos: Difusão em ágar. Antisséptico. Clorexidina. Ensaio microbiológico. Controle de qualidade. Validação.

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Microbiological assay for the determination of meropenem in pharmaceutical dosage form

Cited by 33 publications

References 12 publications

Even Apparently Insignificant Chemical Deviations among Bioequivalent Generic Antibiotics Can Lead to Therapeutic Nonequivalence: the Case of Meropenem

Even Apparently Insignificant Chemical Deviations among Bioequivalent Generic Antibiotics Can Lead to Therapeutic Nonequivalence: the Case of Meropenem

Stability and degradation kinetics of meropenem in powder for injection and reconstituted sample

Development and validation of a microbiological assay for determination of chlorhexidine digluconate in aqueous solution

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