Rapid and Simultaneous Quantitation of Amoxicillin and Clavulanic Acid in Human Plasma and Urine by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Study

Fan, Yaxin; Wu, Xiaojie; Zhao, Miao; Guo, Beining; Cao, Guoying; Yu, Jingwei; Chen, Yuancheng; Zhang, Jing

doi:10.2116/analsci.32.1269

Cited by 10 publications

(4 citation statements)

References 23 publications

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“…The excretion rates of AMO, AMA, and DIKETO in urine from the AS and mixture groups were 10.98 ± 0.65% and 11.68 ± 0.76%, 24.26 ± 1.36% and 23.52 ± 1.04%, and 7.15 ± 0.42% and 8.40 ± 0.62%, respectively, which shows that AMO was excreted in urine mainly as its metabolite AMA. The total excretion rate through urine for both groups was similar to that reported in the literature [54,55]. Acetonitrile, methanol, and formic acid were obtained at chromatographic grade from Thermo Fisher Scientific (China) Co., Ltd. (Shanghai, China).…”

Section: Discussionsupporting

confidence: 72%

A Comprehensive Study to Determine the Residual Elimination Pattern of Major Metabolites of Amoxicillin–Sulbactam Hybrid Molecules in Rats by UPLC–MS/MS

Zhao,

Sun,

et al. 2024

Molecules

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Amoxicillin and sulbactam are widely used in animal food compounding. Amoxicillin–sulbactam hybrid molecules are bicester compounds made by linking amoxicillin and sulbactam with methylene groups and have good application prospects. However, the residual elimination pattern of these hybrid molecules in animals needs to be explored. In the present study, the amoxicillin–sulbactam hybrid molecule (AS group) and a mixture of amoxicillin and sulbactam (mixture group) were administered to rats by gavage, and the levels of the major metabolites of amoxicillin, amoxicilloic acid, amoxicillin diketopiperazine, and sulbactam were determined by UPLC–MS/MS. The residue elimination patterns of the major metabolites in the liver, kidney, urine, and feces of rats in the AS group and the mixture group were compared. The results showed that the total amount of amoxicillin, amoxicilloic acid, amoxicillin diketopiperazine, and the highest concentration of sulbactam in the liver and kidney samples of the AS group and the mixture group appeared at 1 h after drug withdrawal. Between 1 h and 12 h post discontinuation, the total amount of amoxicillin, amoxicilloic acid, and amoxicillin diketopiperazine in the two tissues decreased rapidly, and the elimination half-life of the AS group was significantly higher than that in the mixture group (p < 0.05); the residual amount of sulbactam also decreased rapidly, and the elimination half-life was not significantly different (p > 0.05). In 72 h urine samples, the total excretion rates were 60.61 ± 2.13% and 62.62 ± 1.73% in the AS group and mixture group, respectively. The total excretion rates of fecal samples (at 72 h) for the AS group and mixture group were 9.54 ± 0.26% and 10.60 ± 0.24%, respectively. These results showed that the total quantity of amoxicillin, amoxicilloic acid, and amoxicillin diketopiperazine was eliminated more slowly in the liver and kidney of the AS group than those of the mixture group and that the excretion rate through urine and feces was essentially the same for both groups. The residual elimination pattern of the hybrid molecule in rats determined in this study provides a theoretical basis for the in-depth development and application of hybrid molecules, as well as guidelines for the development of similar drugs.

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Section: Discussionsupporting

confidence: 72%

A Comprehensive Study to Determine the Residual Elimination Pattern of Major Metabolites of Amoxicillin–Sulbactam Hybrid Molecules in Rats by UPLC–MS/MS

Zhao,

Sun,

et al. 2024

Molecules

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“…However, the methods with a shorter analysis time were not sensitive enough for PK studies [11], or showed poor retention of amoxicillin which leads to possible interference by non-retained and co-eluting components [12]. Moreover, sample preparation included time consuming steps by using solid phase extractions [7,11,12,13], or the use of phosphate buffers [14] which is not recommended for MS analysis. Therefore, a more suitable LC-MS/MS method is required with a wide range of quantitation of amoxicillin in both minipig milk and plasma matrices generated from the in vivo study mentioned above.…”

Section: Introductionmentioning

confidence: 99%

Sensitive and rapid method for the quantitation of amoxicillin in minipig plasma and milk by LC-MS/MS: A contribution from the IMI ConcePTION project

Armoudjian¹,

Qi²,

Lammens³

et al. 2023

Journal of Pharmacological and Toxicological Methods

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“…[6][7][8][9] It was used in a study with a 10:1 dose ratio of amoxicillin/clavulanate potassium injection. 10,11 As the concentration difference between amoxicillin and clavulanate increases, so do the demands on the sensitivity and reliability of the detection method. Therefore, in this study, a new ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of amoxicillin and clavulanic acid in human plasma is described.…”

mentioning

confidence: 99%

“…High‐performance liquid chromatography (HPLC), HPLC‐ultraviolet, HPLC‐mass spectrometry, and near‐infrared spectroscopy are typical techniques for determining amoxicillin and clavulanate in human plasma 6‐9 . It was used in a study with a 10:1 dose ratio of amoxicillin/clavulanate potassium injection 10,11 . As the concentration difference between amoxicillin and clavulanate increases, so do the demands on the sensitivity and reliability of the detection method.…”

mentioning

confidence: 99%

Pharmacokinetics of Amoxicillin and Clavulanate Potassium for Suspension (200 mg/28.5 mg) in Healthy Subjects: Sample Add Stabilizer Study and Food Effects

Qin²,

Zhang

et al. 2022

Clinical Pharm in Drug Dev

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The present study compares the pharmacokinetics of amoxicillin and clavulanate potassium suspension (200 mg/28.5 mg) during fasting and postprandial conditions, and the sample adds a stabilizer study. Two randomized, crossover trials were conducted in an open‐label, single‐center study (a fasting trial and a postprandial trial). In each part of the study, the subjects were randomly assigned to receive either test or reference products (200 mg/28.5 mg) in a 1:1:1 ratio, followed by the alternative products after a 7‐day washout period. Plasma amoxicillin and clavulanic acid concentrations were analyzed by liquid chromatography–tandem mass spectrometry. WinNonlin software was used to evaluate the pharmacokinetic parameters (noncompartmental model). The formulations were considered bioequivalent if the geometric means of area under the plasma concentration–time curve (AUC) and maximum plasma concentration (Cmax) of amoxicillin and clavulanic acid were within the predetermined bioequivalence range established by average bioequivalence (ABE) or reference‐scaled ABE. Tolerability was assessed throughout the study. The postprandial trial and the fasting study each had 12 volunteers. Under fasting and postprandial conditions, the 90%CI for the ratio of geometric means of amoxicillin of Cmax, AUC from time 0 to the last measurable concentration, and AUC from time 0 to infinity were within the ABE acceptance limits (80%‐125%); the geometric means of clavulanic acid of Cmax (critbound, –0.03; point estimate, 1.07) were within the reference‐scaled ABE acceptance limits, and the AUC from time 0 to the last measurable concentration and AUC from time 0 to infinity were within the ABE acceptance limits (80%–125%). Time to maximum concentration of amoxicillin was delayed 1.0 hour with high‐fat meals compared to fasting conditions. Meantime, high‐fat meals decreased the exposure of clavulanic acid by nearly 40%. No serious adverse events were found among the subjects. The bioequivalence of test and reference amoxicillin and clavulanate potassium for suspension was validated in this study under fasting and postprandial conditions.

show abstract

Rapid and Simultaneous Quantitation of Amoxicillin and Clavulanic Acid in Human Plasma and Urine by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Study

Cited by 10 publications

References 23 publications

A Comprehensive Study to Determine the Residual Elimination Pattern of Major Metabolites of Amoxicillin–Sulbactam Hybrid Molecules in Rats by UPLC–MS/MS

A Comprehensive Study to Determine the Residual Elimination Pattern of Major Metabolites of Amoxicillin–Sulbactam Hybrid Molecules in Rats by UPLC–MS/MS

Sensitive and rapid method for the quantitation of amoxicillin in minipig plasma and milk by LC-MS/MS: A contribution from the IMI ConcePTION project

Pharmacokinetics of Amoxicillin and Clavulanate Potassium for Suspension (200 mg/28.5 mg) in Healthy Subjects: Sample Add Stabilizer Study and Food Effects

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