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UPLC-MS/MS Method for Simultaneous Determination of 14 Antimicrobials in Human Plasma and Cerebrospinal Fluid: Application to Therapeutic Drug Monitoring.

ABSTRACT: Pharmacokinetics/pharmacodynamics is the foundation for guiding the rational application of antibiotics in clinical practice, so it is necessary to establish quantitative methods for accurate drug concentration determination. This study aimed to develop a rapid and simple ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous quantification of 14 antibiotics (amikacin, etimicin, ceftazidime, cefepime, cefoperazone, ceftriaxone, daptomycin, latamoxef, linezolid, meropenem, biapenem, ampicillin, norvancomycin, and vancomycin) in human plasma and cerebrospinal fluid. Antibiotics were chromatographically separated on a Waters ACQUITY UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) via gradient elution within 3 minutes and were monitored using positive ion fitted with multiple reaction monitoring. The lower limit of quantification was 0.05-2.0 μg·mL^-1. The method was verified according to the FDA bioanalysis method validation guidelines, which showed excellent accuracy (from 86.75% to 110.85%) and precision (from 0.46% to 10.97%). At last, this method was successfully applied to therapeutic drug monitoring in 113 patients under antibiotics treatment.

SUBMITTER: Sun H

PROVIDER: S-EPMC8754666 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Millions of adults have been reported with hyperlipemia in the world. It is still unclear whether the plasma level of essential amino acids (AAs) will be influenced by the hyperlipemia. This study was aimed to investigate the AAs levels and the underlying metabolic relationship in hyperlipidemic subjects. METHODS:An ultra-high performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed for the determination of phenylalanine (Phe), valine (Val), histidine (His), tryptophan (Trp), and methionine (Met). Plasma samples (100??L) were precipitated by acetonitrile (300??L) and analyzed on a BEH C18 (2.1?mm?×?100?mm, 1.7??m) column at 40?°C by gradient elution. The mobile phase composed of 0.1% formic acid and acetonitrile was used with flow rate at 0.2-0.4?ml/0-3?min. Five AAs were determined at positive electrospray ionization (ESI+) at m/z 118.1/72.1 (Val), 150.12/104.02(Met), 156.06/110.05(His), 166.1/120.1(Phe), and 205.2/188.02 (Trp). A total of 75 healthy subjects and 83 hyperlipidemic subjects, who had blood routine test and plasma lipid test were determined by developed UPLC-MS/MS. RESULTS:It was shown that there was good linearity for Val, Met, His, Phe, and Trp within 1-100??g/mL. The relative standard deviations of precision and accuracy were all within 15%. The level of Val, Phe, Trp, His, and Met were 35.34?±?15.64, 22.72?±?9.13, 17.23?±?4.94, 16.78?±?13.64, and 6.24?±?1.97??g/mL in healthy subjects, while they were 38.04?±?16.70, 22.41?±?8.45, 15.62?±?5.77, 18.35?±?14.49, and 6.21?±?1.97??g/mL in hyperlipidemic subjects respectively. The Spearman's correlations analysis showed that there were high correlations between Val, Phe, Trp, His, Met and triglyceride in healthy subjects. While, those correlations decreased in hyperlipemia cases. CONCLUSION:A convenient and sensitive method for simultaneous determination of Val, Phe, Trp, His, and Met in human plasma was developed. There was a high correlation between Val, Phe, Trp, His, Met and triglyceride. Hyperlipemia influences the metabolic balance of His, Phe, Trp, Met and Val.

Project description:Guanjiekang (GJK) that is formed by five medicinal herbs including Astragali Radix, Aconiti Lateralis Radix Praeparaia, Glycyrrhizae Radix et Rhizoma, Corydalis Rhizoma and Paeoniae Radix Alba was used for the treatment of rheumatoid arthritis (RA). However, the pharmacokinetic (PK) profile of active components in GJK remains unclear. This study aims to evaluate the pharmacokinetic behavior of seven representative active constituents in GJK (i.e., benzoylhypaconine, benzoylmesaconine, paeoniflorin, tetrahydropalmatine, calycosin-7-glucoside, formononetin and isoliquiritigenin) after oral administration of GJK in rats. A rapid, sensitive and reliable ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) method has been successfully developed for the simultaneous determination of these seven constituents in rat plasma. Chromatographic separation was achieved on a C18 column with a gradient elution program that consists of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.35 mL/min. Detection was performed under the multiple reaction monitoring (MRM) in the positive electrospray ionization (ESI) mode. The calibration curves exhibited good linearity (R² > 0.99) over a wide concentration range for all constituents. The accuracies ranged from 92.9% to 107.8%, and the intra-day and inter-day precisions at three different levels were below 15%. Our PK results showed that these seven compounds were quickly absorbed after the administration of the GJK product, and Tmax ranged from 30 min to 189 min. The in vivo concentrations of paeoniflorin and isoliquiritigenin were significantly higher than the reported in vitro effective doses, indicating that they could partly contribute to the therapeutic effect of GJK. Therefore, we conclude that pharmacokinetic studies of representative bioactive chemicals after administration of complex herbal products are not only necessary but also feasible. Moreover, these seven compounds that were absorbed in vivo can be used as indicator standards for quality control and for determining pharmacokinetic behavior of herbal medicines in clinical studies.

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UPLC-MS/MS Method for Simultaneous Determination of 14 Antimicrobials in Human Plasma and Cerebrospinal Fluid: Application to Therapeutic Drug Monitoring.

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