A novel reversed-phase high-performance liquid chromatographic assay for the simultaneous determination of imipenem and meropenem in human plasma and its application in TDM

Zou, Le; Meng, Fanqi; Hu, Lin; Huang, Qi; Liu, Min; Yin, Tongming

doi:10.1016/j.jpba.2019.01.039

Cited by 21 publications

(29 citation statements)

References 33 publications

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“…On the one hand, this study confirmed degradation of meropenem at -20 • C in human plasma samples. On the other hand, detailed assessment over 1 year showed that degradation was not yet significant after 3-20 days, as suggested by previous studies [7][8][9][10]. Noteworthy, our results stand in contrast to the findings published by Zander et al [11], who reported substantial decreases of meropenem concentration ≥7 days of storage at −20 • C, with minor amounts remaining after 90-180 days, in serum-based test samples.…”

Section: Discussioncontrasting

confidence: 54%

“…This decrease seemed to compensate for higher relative degradation during the first 100 days. Considering all of the above, meropenem seems to be stable in plasma at −20 • C for longer than the suggested 3-20 days [7][8][9][10].…”

Section: Discussionmentioning

confidence: 84%

“…Even when plasma samples are frozen, there is uncertainty about meropenem long-term stability. Stability at −20 • C has only been demonstrated for 3 days up to 20 days [7][8][9][10]. Mortensen et al [7] recommend that plasma samples for quantification of meropenem stored for longer than 3 days should be kept at −80 • C. To date, stability of meropenem in human plasma at −80 • C has been shown for at least 3-9 months [5,6,11].…”

Section: Introductionmentioning

confidence: 99%

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Meropenem Stability in Human Plasma at −20 °C: Detailed Assessment of Degradation

et al. 2021

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There are concerns about the stability of meropenem in plasma samples, even when frozen at −20 °C. Previous smaller studies suggested significant degradation of meropenem at −20 °C after 3–20 days. However, in several recent clinical studies, meropenem plasma samples were still stored at −20 °C, or the storage temperature and/or time were not mentioned in the paper. The aim of this study was to describe and model meropenem degradation in human plasma at −20 °C over 1 year. Stability of meropenem in human plasma at −20 °C was investigated at seven concentrations (0.44, 4.38, 17.5, 35.1, 52.6, 70.1, and 87.6 mg/L) representative for the range of relevant concentrations encountered in clinical practice. For each concentration, samples were stored for 0, 7, 14, 21, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224, 252, 280, 308, 336, and 364 days at −20 °C before being transferred to −80 °C until analysis. Degradation was modeled using polynomial regression analysis and artificial neural network (ANN). Meropenem showed significant degradation over time in human plasma when stored at −20 °C. Degradation was present over the whole concentration range and increased with higher concentrations until a concentration of 35.1 mg/L. Both models showed accurate prediction of meropenem degradation. In conclusion, this study provides detailed insights into the concentration-dependent degradation of meropenem in human plasma stored at −20 °C over 1 year. Meropenem in human plasma is shown to be stable at least up to approximately 80 days when stored at −20 °C. The polynomial model allows calculating original meropenem concentrations in samples stored for a known period of time at −20 °C.

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Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

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Meropenem Stability in Human Plasma at −20 °C: Detailed Assessment of Degradation

et al. 2021

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“…Meropenem serum concentrations were measured using automatic two-dimensional high-performance liquid chromatography (Demeter Instrument Co., Ltd., Hunan, China). The rst-dimensional chromatographic column was an Aston SNCB (4.6 × 50 mm, 5 µm), and the second-dimensional chromatographic column was an Aston SBN (4.6 × 200 mm, 5 µm) 29,30 . There was an excellent linear relationship between peak area and the concentration range of 0.78 to 58.52 μg/mL.…”

Section: Sampling and Assaysmentioning

confidence: 99%

Does prolonged infusion time really improve the efficacy of meropenem therapy? A prospective study in critically ill patients

Zhao

Zou

Xiao

et al. 2021

Preprint

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Background: Meropenem is a carbapenem antibiotic that has demonstrated excellent in vitro activity against gram-negative clinical isolates and is commonly used in critically ill patients. This study aimed to find the pharmacokinetic/ pharmacodynamic of meropenem in critically ill patients and whether prolonged injection duration is really beneficial to meropenem therapy. Method: We included 209 samples in 64 patients in this prospective study. PPK analysis and Monte Carlo dosing simulations were developed using Phoenix.Results: A two-compartment model described the data adequately. Clearance (CL), volume (V), clearance of peripheral compartment (CL2), volume of peripheral compartment (V2) were 6.15 L/h, 2.83 L/h, 17.40L, and 17.48L, respectively. Creatinine clearance and uric acid were significant covariates. Patients with creatinine clearance of 60 ml/min or less and uric acid greater than 400 μmol/l could achieve the target > 90% under the minimum inhibitory concentration (MIC) of 8 mg/L, even with the administration dose of 500 mg/8 h with a 2-h infusion. Prolonging the infusion time significantly improved the therapeutic effect when MIC＜4. However, for the pharmacodynamic (PD) effects of 100% fT > MIC and 100% fT > 4MIC, no significant statistical difference was observed in critically ill patients.Conclusions: Critically ill patients with lower creatinine clearance and higher uric acid levels were likely to need a lower dosage of meropenem. Prolonged infusion time were not always beneficial for those who need a higher therapeutic target (100% fT > MIC,100% fT > 4 MIC) or with MIC 4mg/L. Increasing dose or alternative therapeutic strategies may be required for critically ill patients with drug-resistant or severe infections. The study is of great significance to guide the rational use of meropenem in critically ill patients.Trial registration: The trial was registered in the China Clinical Trial (ChiCTR1900020672). Registered on 12 January 2019.

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“…Objective function values (OFV) were used to compare the model t. Covariates were retained in the model if the additional covariates were signi cant at a P-value of 0.01 (△OFV > 6.635). VPC was used to evaluate the goodness of t [12,[29][30][31][32].…”

Section: Pharmacokinetic Studymentioning

confidence: 99%

Effects of uric acid, creatinine clearance, and infusion duration on the population pharmacokinetics of meropenem in critically ill patients

Zhao

Zou

Xiao

et al. 2021

Preprint

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Background Meropenem is a carbapenem antibiotic that has demonstrated excellent in vitro activity against gram-negative clinical Isolates and is commonly used in critically ill patients. This study aimed to describe the population pharmacokinetics (PPK) of meropenem and determine the optimal dosage in these patients. Method: We included 209 samples in 64 patients in this prospective study. PPK analysis and Monte Carlo dosing simulations were developed using Phoenix. Results A two-compartment model described the data adequately. Clearance (CL), volume (V), clearance of peripheral compartment (CL2), volume of peripheral compartment (V2) were 6.15 L/h, 2.83 L/h, 17.40L, and 17.48L, respectively. Creatinine clearance and uric acid were significant covariates. Patients with creatinine clearance of 60 ml/min or less and uric acid greater than 400 µmol/l could achieve the target >\(\)90% under the minimum inhibitory concentration (MIC) of 8 mg/L, even with the administration dose of 500 mg/8 h with a 2-h infusion. Prolonging the infusion time significantly improved the therapeutic effect when MIC༜4. However, for the pharmacodynamic (PD) effects of 100% fT > MIC and 100% fT > 4MIC, no significant statistical difference was observed in critically ill patients. Conclusions Critically ill patients with lower creatinine clearance and higher uric acid levels were likely to need a lower dosage of meropenem. Prolonged infusion time were not appear to be beneficial for those who need a higher therapeutic target (100% fT > MIC,100% fT > 4 MIC) or with MIC\(>\)4mg/L. Increasing dose or alternative therapeutic strategies may be required for critically ill patients with drug-resistant or severe infections. The study is of great significance to guide the rational use of meropenem in critically ill patients. Trial registration: The trial was registered in the China Clinical Trial (ChiCTR1900020672). Registered on 12 January 2019.

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A novel reversed-phase high-performance liquid chromatographic assay for the simultaneous determination of imipenem and meropenem in human plasma and its application in TDM

Cited by 21 publications

References 33 publications

Meropenem Stability in Human Plasma at −20 °C: Detailed Assessment of Degradation

Meropenem Stability in Human Plasma at −20 °C: Detailed Assessment of Degradation

Does prolonged infusion time really improve the efficacy of meropenem therapy? A prospective study in critically ill patients

Effects of uric acid, creatinine clearance, and infusion duration on the population pharmacokinetics of meropenem in critically ill patients

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