Method for determining concentrations of vancomycin and degradation product in human serum

A vancomycin and degradation product technology, applied in the detection of drug concentration in human serum, vancomycin and crystalline degradation product CDP-1 concentration field, can solve the problem of inability to quantify degradation products separately, difficult to meet TDM requirements, difficult to separate standards It can achieve the effect of good recovery rate, low cost and easy operation.

Pending Publication Date: 2020-05-05
AFFILIATED HUSN HOSPITAL OF FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the wide range of sources of TDM blood samples, it was found that the HPLC method was easily affected by miscellaneous peaks, etc. in the TDM detection of the application, resulting in large deviations in the measurement results; The standard product of CDP-1 contains a certain amount of vancomycin. Since CDP-1-m, vancomycin and CDP-1-M are all hydrophilic compounds with close polarities, it is difficult to separate pure standard products. It is still necessary to quantify the contents of the three compounds in

Method used

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  • Method for determining concentrations of vancomycin and degradation product in human serum
  • Method for determining concentrations of vancomycin and degradation product in human serum
  • Method for determining concentrations of vancomycin and degradation product in human serum

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Instruments, materials and reagents:

[0046] Instrument: Waters liquid chromatograph, equipped with Waters 2487 ultraviolet detector and Empower data acquisition and processing software, Waters Corporation of the United States;

[0047] Materials and reagents: CDP-1 standard product, batch number 1-TMH-108-1, purchased from Canada TRC Company; vancomycin, specification 1007u / mg, batch number 130360-201302, purchased from China Institute for the Control of Pharmaceutical and Biological Products; Potassium hydrogen and phosphoric acid, analytically pure, were purchased from Lingfeng Reagent Co., Ltd.; acetonitrile, chromatographically pure, purchased from Sigma-Aldrich; ultrapure water, freshly prepared daily by Milli-Q;

[0048] Experimental part:

[0049] Solution preparation: Accurately weigh an appropriate amount of CDP-1 standard substance into a 5mL volumetric flask, add ultrapure water to prepare a 1053μg / mL stock solution. Use 5% acetonitrile water to dilute to...

Embodiment 2

[0055] Instruments, materials and reagents:

[0056] Instrument: Shimadzu LC-30AD ultra-high performance liquid chromatography (Shimadzu, Japan) in series with API5500 triple quadrupole mass spectrometer (AB SCIEX, USA), equipped with electrospray ionization source (ESI); data acquisition and processing software is Analyst1. 6.2; temperature-controlled high-speed centrifuge (Thermo Fisher, Germany); electronic analytical balance (Mettler, Switzerland);

[0057] Materials and reagents: CDP-1 standard product, batch number 1-TMH-108-1, purchased from Canada TRC Company; vancomycin, specification 1007u / mg, batch number 130360-201302, internal standard norvancomycin, purity 83.4% , batch number 130338-200303, were purchased from China National Institute for the Control of Pharmaceutical and Biological Products; acetonitrile and formic acid (chromatographically pure) were purchased from Sigma-Aldrich Company; ultrapure water was freshly prepared daily with Milli-Q; blank serum was ...

Embodiment 3

[0086] Example 3 Clinical application

[0087] Twelve hemodialysis patients (6 males and 6 females) were selected for the treatment of Gram-positive bacterial infections requiring vancomycin and TDM. Samples of trough concentrations were collected no earlier than before the second dose of administration, and 0.5- The peak concentration samples were collected in 1 hour, and the whole blood samples were centrifuged at 3000rpm for 10 minutes, and the supernatant was taken and frozen in a -70°C refrigerator for testing. The demographic characteristics and concentration data of the patients are shown in Table 9. , the ratio of CDP-1 (CDP-1-m+CDP-1-M) to vancomycin concentration is 5.9%-22.9% and 5.1%-12.2%, respectively, if there is an interaction of CDP-1 in the detection method, or Failure to separate vancomycin and CDP-1 may lead to inaccurate dose adjustment in 2 patients (16.7%), thus affecting the individualized precise drug administration of patients.

[0088] Table 9 Demog...

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Abstract

The invention belongs to the technical field of drug concentration monitoring, and relates to a method for simultaneously determining concentrations of vancomycin and a crystalline degradation productCDP-1 in human serum by LC-MS/MS. According to the method, norvancomycin is used as an internal standard, formic acid is used for acidifying serum, quantitative acetonitrile precipitated protein is added, acetonitrile and formic acid water are used as mobile phases, and the concentrations of human serum vancomycin and CDP-1 are determined through an LC-MS/MS method. According to the method, the sampling amount is small, and pretreatment is simple and rapid. The method can be used for determining the concentrations of vancomycin and degradation products CDP-1 in serum samples of conventional clinical patients. Particularly, different degrees of CDP-1 generated after hemodialysis of patients with renal insufficiency can be quantified, so that the concentration of the antibacterial active ingredient vancomycin is reduced, an individualized vancomycin dosing scheme can be made and adjusted clinically, the clinical curative effect and the bacterial clearance rate can be improved, the generation of bacterial drug resistance is reduced, and toxic and side effects such as renal toxicity and the like are reduced.

Description

technical field [0001] The invention belongs to the technical field of drug concentration monitoring, and relates to a method for detecting drug concentration in human serum, in particular to the simultaneous determination of vancomycin and crystalline degradation product CDP in human serum based on liquid chromatography-tandem mass spectrometry (LC-MS / MS) -1 (including 2 kinds of metabolites CDP-1-m and CDP-1-M) concentration method. Background technique [0002] According to data records, the glycopeptide antibiotic vancomycin has been used in clinical practice for 60 years, and it is mainly used to intervene in infections caused by Gram-positive bacteria. Drug of choice. Medical practice shows that the pharmacokinetics of vancomycin varies greatly among individuals, the safety range is small, the therapeutic window is narrow, and adverse reactions such as nephrotoxicity and ototoxicity often occur. Therefore, therapeutic drug concentration monitoring (TDM) is recommended...

Claims

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Application Information

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IPC IPC(8): G01N30/02
CPCG01N30/02
Inventor 范亚新陈渊成张菁郁继诚彭小林
Owner AFFILIATED HUSN HOSPITAL OF FUDAN UNIV
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