Bioassay Applied to Quantitative Determination of Doripenem in Powder for Injection – Method Validation and Degradation Kinetics Study

Führ, Fernanda; Paliosa, Patrícia Klitzke; Costa, M.; Garcia, Cássia Virgínia; Schapoval, Elfrides E.S.; Steppe, Martin; Mendez, Andreas Sebastian Loureiro

doi:10.2174/1573412911309030003

Cited by 6 publications

(8 citation statements)

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“…Previous literature indicated that carbapenems are very susceptible to thermic and humidity conditions, with a high rate of decomposition along the storage time (Mendez et al, ; Smith et al, ; Zajac et al, ). Recently, Fuhr et al () reported a bioassay for quantitation of doripenem in which the reaction kinetics was determined (apparent zero‐order) for thermal and photolytic degradation. Our experience with carbapenems demonstrated that kinetic behavior varies depending on drug matrix (media) and degradation factor (strength).…”

Section: Resultsmentioning

confidence: 99%

Stability of doripenem in reconstituted solution – thermal and oxidative decomposition kinetics and degradation products by LC–MS

Barbosa

Cassol

Batista

et al. 2017

Biomedical Chromatography

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A ultra-fast liquid chromatography method applied to quantitation of doripenem in powder for injection was validated. Validation parameters were assayed and a rapid analysis was established by a reversed-phase system comprising a C column endcapped (50 × 4.0 mm, 2.0 μm), mobile phase consisting of phosphoric acid 0.01% (pH 3.8) and acetonitrile (98:02, v/v) and a flow rate of 0.4 mL min . Drug stability was studied through submission to forced conditions, allowing the major degradation products to be detected and the kinetics parameters to be established. Thermal and oxidative degradation were determined, and indicated a kinetic decomposition following first and second order, respectively. The main degradation products were identified by LC-MS analysis, and the results were evaluated in order to suggest the chemical structures corresponding to respective masses and fragmentations. Six compounds were identified, with m/z 411, 427, 437, 634, 650 and 664. All of them resulted from cleavage of β-lactam ring and alcoholic chain and/or dimerization. These experimental results provide valuable information about the stability of doripenem reconstituted solution and procedures for its handling and storage.

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Section: Resultsmentioning

confidence: 99%

Stability of doripenem in reconstituted solution – thermal and oxidative decomposition kinetics and degradation products by LC–MS

Barbosa

Cassol

Batista

et al. 2017

Biomedical Chromatography

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“…Degradation kinetics studies are also complementary and help to determine the influence of extrinsic and intrinsic factors in the decomposition rate (velocity; Carstensen & Rhodes, ). Several works have reported kinetics aspects during drug stability assays, involving drug monitoring in controlled decomposition conditions (heat, hydrolysis, photolysis, oxidation) and calculating kinetic order and related parameters (Barbosa et al, ; Fuhr et al, ; Mendez et al, ; Mendez, Chagasteles, Palma, Nardi, & Schapoval, ).…”

Section: Resultsmentioning

confidence: 99%

“…Thermal, photolytic and oxidative degradation kinetics were studied by applying the graphical method by plotting the drug concentration, the log of concentration and the reciprocal concentration vs. time, which indicate the zero‐order, first‐order and second‐order rate, respectively (Fuhr et al, ; Mendez, Dalomo, Steppe, & Schapoval, ; Nudelman, ). For each curve, the correlation coefficient ( r ) was obtained and the best fit indicates the reaction order.…”

Section: Methodsmentioning

confidence: 99%

Stability, degradation impurities and decomposition kinetics for paliperidone from osmotic tablets

Cassol

Barbosa

Garcia

et al. 2018

Biomedical Chromatography

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The antipsychotic paliperidone was investigated with a focus on stability, degradation impurities and kinetics reaction profile. Osmotic tablets 3 mg (OROS ) were subjected to extraction in an ultrasonic bath and the resulting acidic solution was stressed by forced conditions. Degraded samples were monitored by HPLC-DAD in different storage times for acidic and alkaline hydrolysis, oxidation, heat and photolysis. Photolysis was shown to be a strong degradation factor, with a drug content of 24.64% remaining after 24 h. Oxidation (H O 18%) caused a slow decomposition, with a drug content of 83.49% remaining after 72 h. Through kinetics graphics, first-order reactions were found for oxidation, heat and photolysis. By UPLC-MS analysis, the degraded matrix could be investigated for identification of impurities with m/z 445.3128, m/z 380.8906, m/z 364.9391, m/z 232.9832 and m/z 217.0076, allowing the identification of derivatives N-oxide and with modifications in the lactam, benzisoxazole and pyrimidine rings. Paliperidone in liquid state, like analytical solutions or formulation, must be carefully handled to avoid drug exposure, specially in storage conditions.

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“…Therefore, microbiological assays can be an alternative to the physicochemical methods like HPLC, not requiring sophisticated equipment or toxic solvents, and being viable to use even in small laboratories. For carbapenems, two microbiological cylinder-plate assays are described for meropenem and doripenem, both developed to determine the drugs in powder for injections (13,19). For imipenem, this methodology is absent.…”

Section: Drug Analytical Researchmentioning

confidence: 99%

“…Drug Anal Res, 2018; 02, 08-13 The linear regression analysis performed by ANOVA (analysis of variance) was used to prove the linearity performance, and not shown deviations from parallelism or significant differences from the medium values (p-value > 0.05), as recommended in official guidelines (17,19). The Table 1 illustrates the ANOVA applied to results of third day of analysis, considering results from 24 plates (equivalent to three assays with 8 plates).…”

Section: Drug Analytical Researchmentioning

confidence: 99%

Microbiological Assay for Quantitative Determination of Imipenem in Powder for Injection

et al. 2018

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This work describes the development and validation of a microbiological method using the cylinder-plate assay for quantitative determination of imipenem in powder for injection. The aim was to obtain a low-cost and suitable methodology that can be alternative to physicochemical techniques already described, contributing for the quality control of this antibiotic. Firstly, the analytical conditions were optimized, testing the microorganism, inoculum concentration and best range of sample and standard concentrations, in a way that provides the adequate measurement of the inhibition halos. Staphylococcus epidermidis ATCC 12228 was selected as test microorganism, as well as 2.0 % of inoculum concentration. The validation protocol followed the official guidelines, and the parameters evaluated were linearity, precision (intermediate precision and repeatability) and accuracy. All standard curves ranging 0.5-2.0 µg/mL showed r values higher than 0.999, and ANOVA confirmed that were no deviation from linearity (p-value > 0.05). The method also proved to be precise with RSD (relative standard deviation) values ranging 0.28-0.64 for repeatability and 2.49 for intermediate precision. It was performed three days of experiments, being three assays of eight plates a day. The drug mean content was 101.05%. Accuracy was assessed by recovery test, with standard recovery percentage of 101.70-107.90% (mean recovery = 104.86%), which was considered satisfactory. Therefore, the proposed microbiological method was considered validated and suitable for application in quantitative determination of this drug, being useful for quality control routine.

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Bioassay Applied to Quantitative Determination of Doripenem in Powder for Injection – Method Validation and Degradation Kinetics Study

Cited by 6 publications

References 0 publications

Stability of doripenem in reconstituted solution – thermal and oxidative decomposition kinetics and degradation products by LC–MS

Stability of doripenem in reconstituted solution – thermal and oxidative decomposition kinetics and degradation products by LC–MS

Stability, degradation impurities and decomposition kinetics for paliperidone from osmotic tablets

Microbiological Assay for Quantitative Determination of Imipenem in Powder for Injection

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