Kinetics and Mechanism of Degradation of Cefotaxime Sodium in Aqueous Solution

Berge, S.M.; Henderson, Nathaniel L.; Frank, M.

doi:10.1002/jps.2600720114

Cited by 44 publications

(16 citation statements)

References 8 publications

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“…The degradation of CFX followed pseudo ® rst-order kinetics, also as previously shown (Berge et al 1983, Fabre et al 1984, where the rate constant in bu er solution at pH 1.0, kB, was determined to be 0.048 h 1 at 30 ë C (table 5). Incorporating CFX in DMPC liposomes, or DMPC:CHOL liposomes ranging from 20:1 to 1:1 mole ratio did not signi® cantly change kB up to 36 h. The micrographic results of the interaction of CFX with DMPC liposomes are shown in ® gure 6a± d. The dense population of liposomes in the absence of CFX can be seen in ® gure 6a and this was consistent for more than 60 h at pH 1.0 and 40 ë C. Similarly, in the presence of 7.5 mm CFX the population of liposomes after 10 min was barely changed (® gure 6b).…”

Section: Re Su Ltssupporting

confidence: 59%

Solubilization of liposomes by weak electrolyte drugs II. Cefotaxime

Rogers

Habib

1999

Journal of Microencapsulation

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The solubilization of dimyristoylphosphatidylcholine (DMPC) liposomes by the weak electrolyte drug, cefotaxime (CFX), has been studied as a function of pH, DMPC, temperature, presence of cholesterol (CHOL), and method of liposome preparation. At 7.5 mM CFX the lag time for solubilization increased, the rate of solubilization decreased, and the minimum turbidity reached increased as a function of DMPC at pH 1.0 and 40 degrees C. Solubilization was most pronounced at pHs below the pKa but inhibited at least one pH unit above the pKa. The critical mole ratio of unionized CFX:DMPC, Rec, for solubilization was estimated to be 0.12. Reducing the temperature slowed the rate of solubilization as did the addition of CHOL. Encapsulation of CFX in liposomes did not significantly reduce CFX degradation,. k1 = 0.048 h-1 at 40 degrees C and a complex of DMPC and a degradation product of CFX precipitated as rectangular crystals. As a result, an increase in the turbidity of solubilized systems was observed from about 20 h to 48 h depending on the conditions. Liposomes in the gel state or with at least 20% CHOL did not undergo an apparent reversal of solubilization. It is concluded that the inclusion of weak electrolyte drugs existing predominantly as the unionized species in liquid crystalline state liposomes may undergo a slow solubilization process not necessarily recognized during characterization.

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Section: Re Su Ltssupporting

confidence: 59%

Solubilization of liposomes by weak electrolyte drugs II. Cefotaxime

Rogers

Habib

1999

Journal of Microencapsulation

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“…At appropriate time intervals, samples were withdrawn, cooled with iced water, and immediately analyzed for the remaining cefotaxime sodium using the HPLC method and equipment described in section Analysis of Cefotaxime Sodium . The HPLC method described by previous investigators26 was modified and validated to obtain accurate, sensitive, and precise procedure. All experiments were carried out in duplicate.…”

Section: Methodsmentioning

confidence: 99%

“…A μ‐Bondapack C18 column (4.6 × 250 mm 2 ) obtained from Waters Associates (Massachusetts) was used for this separation. The HPLC method described by previous investigators26 was modified and used in this study. Berge et al26 procedure was carried out using a μ‐Bondapack C18 column (3.9 × 300 mm 2 ) with a methanol–phosphate buffer (pH 7.5; 12:88) mobile phase and a flow rate of 1.2–1.3 mL/min.…”

Section: Methodsmentioning

confidence: 99%

Determination of Solid-State Acidity of Chitin–Metal Silicates and their Effect on the Degradation of Cephalosporin Antibiotics

Gana

Rashid

Badwan

et al. 2012

Journal of Pharmaceutical Sciences

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“…. 48 Our study focuses on three β-lactams: mecillinam, aztreonam and cefotaxime (Fig 1) 49 which have previously been shown to have stability maxima at pH 4-6 [34][35][36]. 50 Mecillinam (also known as amdinocillin or FL1060) is an amidinopenicillin that binds 51 selectively to the PBP2 transpeptidase, inhibiting peptidoglycan synthesis during the 52 elongation phase of bacterial growth.…”

mentioning

confidence: 99%

“…Its degradation 57 has been shown to be highly pH-sensitive in aqueous solution, with a maximum half-life 58 at pH 5 (at 37 • C) of around 200 hours [16]. Aztreonam ( Fig 1B) is a synthetic degradation of cefotaxime has been found to be strongly affected by solvolytic, hydrogen 71 ion and hydroxide ion catalysis, with maximum stability at pH 4.5 -6.5 (at 25 • C) in 72 aqueous solution [36]. 73 Our results show that mecillinam is rather unstable in both MOPS-based media and 74 in LB (S3 Fig), but that (for MOPS media) its stability can be enhanced by adjusting 75 the pH and temperature without excessively compromising bacterial growth.…”

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confidence: 99%

Stability of β-lactam antibiotics in bacterial growth media

Brouwers

Vass

Dawson

et al. 2020

Preprint

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Laboratory assays such as MIC tests assume that antibiotic molecules are stable in the chosen growth medium -but rapid degradation has been observed for antibiotics including β-lactams under some conditions in aqueous solution. Degradation rates in bacterial growth medium are less well known. Here, we develop a 'delay time bioassay' that provides a simple way to estimate antibiotic stability in bacterial growth media. We use the bioassay to measure degradation half-lives of the β-lactam antibiotics mecillinam, aztreonam and cefotaxime in widely-used bacterial growth media based on MOPS and Luria-Bertani (LB) broth. We find that mecillinam degradation can occur rapidly, with a half-life as short as 2 hours in MOPS medium at 37 • C and pH 7.4, and 4-5 hours in LB, but that adjusting the pH and temperature can increase its stability to a half-life around 6 hours without excessively perturbing growth. Aztreonam and cefotaxime were found to have half-lives longer than 6 hours in MOPS medium at 37 • C and pH 7.4, but still shorter than the timescale of a typical minimum inhibitory concentration (MIC) assay. Taken together, our results suggest that care is needed in interpreting MIC tests and other laboratory growth assays for β-lactam antibiotics, since there may be significant degradation of the antibiotic during the assay.Antibiotic efficacy is usually quantified by the minimal inhibitory concentration (MIC), 2 or the concentration of antibiotic needed to prevent bacterial growth over 24 hours in a 3 standard laboratory growth medium [1]; the MIC value plays a central role in 4 diagnostic and therapeutic decision-making. When performing an MIC assay, one 5 assumes that the antibiotic does not degrade over the timescale of the assay. Antibiotic 6 stability is also assumed in a host of other bacterial growth assays that are used to 7 determine antibiotic mechanism of action [2][3][4][5], interactions between antibiotics [6-9], 8 and evolution of antibiotic resistance [10][11][12][13][14]. 9Antibiotic degradation in aqueous solution has been extensively studied in the 10 chemical literature [15][16][17][18][19], and it is well-known that, under some conditions, 11 antibiotics can degrade on timescales much shorter than a typical bacterial growth assay. 12 There has been little work, however, on how quickly antibiotics degrade in standard 13 laboratory growth media, such as those used for MIC assays. Here, we develop a 14 'delay-time bioassay', based on growth measurements in a plate reader, that allows 15 simple estimation of the rate of antibiotic degradation in bacterial growth media. 16Bacterial growth media are chemically complex, since bacterial proliferation requires 17 carbon, nitrogen, phosphorous, iron and a diverse array of micronutrients [20,21]. 18April 14, 2020 1/18 "Undefined" growth media contain ingredients such as yeast extract, blood or beef 19 extract, whose detailed chemical composition is not known. Luria-Bertani (LB) medium, 20 which consists of water, tryptone, sodium chloride and yeast extract, i...

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Kinetics and Mechanism of Degradation of Cefotaxime Sodium in Aqueous Solution

Cited by 44 publications

References 8 publications

Solubilization of liposomes by weak electrolyte drugs II. Cefotaxime

Solubilization of liposomes by weak electrolyte drugs II. Cefotaxime

Determination of Solid-State Acidity of Chitin–Metal Silicates and their Effect on the Degradation of Cephalosporin Antibiotics

Stability of β-lactam antibiotics in bacterial growth media

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