An LC–MS–MS method for the simultaneous quantification of amoxicillin and clavulanic acid in human plasma and its pharmacokinetic application

Gaikwad, Avinash S; Gavali, S.R.; Narendiran,; Katale, Deepak; Bonde, Shantaram; Bhadane, Ranjana P.

doi:10.1016/j.jopr.2013.07.019

Cited by 8 publications

(8 citation statements)

References 12 publications

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“…Amoxicillin is one of the most common semi synthetic antibiotics with broad antibacterial spectrum. The half-life of amoxicillin is about 60 minutes in human [ 1 ]. Therefore, the routine regimen using conventional dosage forms requires three or four times of drug administration a day to keep the plasma drug levels in an effective range [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling

Chai

Yang

et al. 2016

PLoS ONE

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BackgroundAmoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients’ compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages.MethodsThe pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box–Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®.Results and DiscussionSingle factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box–Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry® film to produce pulsatile tablet of amoxicillin. In vitro release study firstly indicated a three-pulse release profile of the tablet. Later the pulse tablet was found to generate the sustained release of amoxicillin in beagle dogs. Furthermore, the Simcyp® software was used to simulate the in vivo concentration time curve model of the three-pulse release tablet for amoxicillin in both human and beagle dog. The prediction by PBPK model nicely fitted the observation in human and beagle dog.ConclusionsThis study has demonstrated the interrelation of factors affecting the pulsatile formulation of amoxicillin using a Box–Behnken design. The three-pulse release tablets of amoxicillin were proven to generate pulsatile release in vitro and sustained release in vivo. This formulation was also found to extend the effective plasma concentration in human compared to the tablet of immediate release based on the simulation data by PBPK modeling. This study provides an example of using PBPK to guide the development of pulsatile dosage forms.

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Section: Introductionmentioning

confidence: 99%

A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling

Chai

Yang

et al. 2016

PLoS ONE

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“…Reyns et al [ 9 ] also confirmed this claim after testing HLB columns. Gaikwad et al [ 8 ] developed a clavulanic acid determination method using HLB extraction procedure but with recovery of only about 50%.…”

Section: Resultsmentioning

confidence: 99%

“…In the available literature, most of the developed tandem mass spectrometric methods for clavulanic acid determination are in human plasma with LOD = 20 μg·L −1 [ 6 ] and LOQ = 25–62 μg·L −1 [ 6 – 8 ]. Of the animal plasma methods, there were published methods for calf plasma with LOD = 3.5 μg·L −1 , LOQ = 25 μg·L −1 [ 9 ], and cat plasma with LOD = 9 μg·L −1 , LOQ = 30 μg·L −1 [ 10 ].…”

Section: Resultsmentioning

confidence: 99%

“…LLOQ and the recovery were 50 μg·L −1 and 97.9–102.4%. Gaikwad et al [ 8 ] developed a clavulanic acid determination method performed on triple quadrupole with chromatographic separation on a C18 column. Human plasma samples were loaded on Oasis HLB SPE columns.…”

Section: Introductionmentioning

confidence: 99%

“…For reliable quantitative analysis, it is important to find the appropriate internal standard; in the studies mentioned above, terbutaline [ 6 ], clenbuterol [ 7 ], ampicillin [ 8 ], and tazobactam were used [ 9 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Mass spectrometric identification and quantification of the antibiotic clavulanic acid in broiler chicken plasma and meat as a necessary analytical tool in finding ways to increase the effectiveness of currently used antibiotics in the treatment of broiler chickens

et al. 2021

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Clavulanic acid is a molecule with antimicrobial effect used in several livestock species treatment. Its inclusion in the treatment of infectious diseases of broilers requires determination of pharmacokinetic and pharmacodynamic parameters in order to determine the appropriate dosage for broilers and ensure safety of chicken products for human health. The present study describes the optimisation of analytical LC-MS/MS method for identification and quantification of clavulanic acid in broiler chicken plasma and meat. The limit of detection and the limit of quantification for the developed method were 3.09 μg·L−1 and 10.21 μg·L−1 for plasma and 2.57 μg·kg−1 and 8.47 μg·kg−1 for meat. The recoveries of the developed plasma and tissue extraction procedure were > 105.7% and > 95.6%, respectively. The achieved coefficient of variation of within-run precision ranged from 2.8 to 10.9% for plasma and from 6.5 to 8.5% for meat. The pharmacokinetic experiment was performed in 112 Ross broiler chickens assigned into time interval groups ranging from 10 min to 24 h in accredited animal facilities. Administered dose of clavulanic acid was 2.5 mg·kg−1 according to the manufacturer’s recommendations. The pharmacokinetic parameters obtained from the experiment are as follows: Cmax = 1.82 ± 0.91 mg·L−1, Tmax = 0.25 h, T1/2 = 0.87 h, Kel = 0.80 ± 0.04 h−1, AUC0-∞ = 2.17 mg·h ·L−1.

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Validation and Application of a Dried Blood Spot Amoxicillin Assay

Page-Sharp,

Yoo,

Salman

et al. 2024

Chromatographia

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Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK) investigations in situations where venous blood sampling is logistically and/or ethically challenging. The aim of this study was to establish, validate and demonstrate the application of a DBS amoxicillin assay for PK studies in vulnerable populations. The matrix effect, process efficiency (84–104%) and recovery (85–110%) of the liquid chromatography–mass spectrometry (LC–MS/MS) assay for amoxicillin in DBS was determined at 1, 10 and 100 µg/mL, and three different haematocrits. Thermal stability studies of amoxicillin in DBS were performed and a bridging study comprising 26 paired plasma and DBS samples was conducted in four healthy individuals. The limits of detection and quantification were 0.02 and 0.05 µg/mL for plasma and DBS amoxicillin assays, respectively. Accuracy and interday precision of amoxicillin in DBS (0.1–100 µg/mL) were 88–103% and 4.5–9.2%, respectively. At room temperature (22 °C) and 4 °C, amoxicillin was stable in DBS for ≈4 and 26 h, respectively. There was no degradation of amoxicillin in DBS at −20 °C for > 6 months. When comparing DBS and plasma collected from healthy volunteers, the slope of the Deming regression was 0.74. Amoxicillin CL/F estimates from DBS and plasma concentration data were 40.8 and 30.7 L/h/70 kg, respectively; V/F was 43.2 and 37.4 L/70 kg, respectively. In conclusion, amoxicillin can be reliably assayed from DBS in research studies but may have limited application in therapeutic drug monitoring. Due to poor stability at room temperature, amoxicillin DBS samples should be promptly dried and placed in frozen storage.

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An LC–MS–MS method for the simultaneous quantification of amoxicillin and clavulanic acid in human plasma and its pharmacokinetic application

Cited by 8 publications

References 12 publications

A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling

A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling

Mass spectrometric identification and quantification of the antibiotic clavulanic acid in broiler chicken plasma and meat as a necessary analytical tool in finding ways to increase the effectiveness of currently used antibiotics in the treatment of broiler chickens

Validation and Application of a Dried Blood Spot Amoxicillin Assay

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