Method for simultaneously determining blood concentrations of six first-line antituberculosis drugs and antifungal drugs voriconazole in blood plasma

An antifungal drug, voriconazole blood technology, applied in the field of clinical blood drug concentration monitoring and control

Pending Publication Date: 2021-02-05
中国人民解放军总医院第八医学中心
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the treatment plan for tuberculosis is the long-term combine...

Method used

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  • Method for simultaneously determining blood concentrations of six first-line antituberculosis drugs and antifungal drugs voriconazole in blood plasma
  • Method for simultaneously determining blood concentrations of six first-line antituberculosis drugs and antifungal drugs voriconazole in blood plasma
  • Method for simultaneously determining blood concentrations of six first-line antituberculosis drugs and antifungal drugs voriconazole in blood plasma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] In this experiment, 7 kinds of antibiotic drugs (isoniazid, rifampicin, rifapentine, ethambutol, pyrazinamide, levofloxacin, voriconazole) standard substances and blank plasma were used to prepare the standard curve, and calculated according to the standard curve The drug concentration in the patient's plasma was obtained.

[0063] 1. Experimental instruments and reagents are as follows:

[0064] Instruments: ABSCIEX 3200QTRAP triple quadrupole tandem mass spectrometer (AppliedBiosystemInc, USA); Prominence LC-20A ultra-fast high performance liquid chromatography system (Shimadzu Technologies Inc., Japan); VDRTEX-5 vortex mixer (Qi Linbeier Instrument Manufacturing Co., Ltd. ); Type 5420 desktop high-speed centrifuge (Eppendorf, Germany).

[0065] Reagents: Isoniazid (National Institute for the Control of Pharmaceutical and Biological Products, batch number 100578-201501); rifampicin (National Institute for the Control of Pharmaceutical and Biological Products, batch n...

Embodiment 2

[0114] This embodiment is basically the same as Example 1, the difference is that the elution procedure is different, and the elution procedure of the present embodiment is:

[0115] time mobile phase A mobile phase B 0-2.5min 92%→80% 8%→20% 2.5-5min 71%→42% 29%→57% 5-7.3min 42% 58% 7.3-10min 27% 73% 10-13min 92% 8%

Embodiment 3

[0117] This embodiment is basically the same as Example 1, the difference is that the elution procedure is different, and the elution procedure of the present embodiment is:

[0118] time mobile phase A mobile phase B 0-2.5min 97%→85% 3%→15% 2.5-5min 76%→47% 24%→53% 5-7.3min 47% 53% 7.3-10min 32% 68% 10-13min 97% 3%

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Abstract

The invention discloses a method for simultaneously determining blood concentrations of six first-line antituberculosis drugs and antifungal drugs voriconazole in blood plasma, and relates to the technical field of clinical blood concentration monitoring and control. According to the method, an HPLC MS/MS method is adopted, acetaminophen is used as an internal standard, the blood plasma is subjected to protein precipitation through using methyl alcohol, is subjected to elution and separation through HPLC under the specific gradient elution condition according to a specific mobile phase, then enters a mass spectrum system and undergoes multi-reaction monitoring and analysis, therefore, accurate quantification of the blood concentration of seven antibiotics is achieved at the same time. Themethod has the advantages of strong specificity, high sensitivity, good precision and accuracy, good stability, high extraction recovery rate, no obvious matrix effect, simple operation, convenience and rapidness. The method provided by the invention can realize high-throughput determination of clinical samples of tuberculosis patients and guide clinical individualized medication.

Description

technical field [0001] The invention relates to the technical field of clinical blood drug concentration monitoring and control, in particular to a method for simultaneously measuring blood drug concentrations of six first-line anti-tuberculosis drugs and antifungal drug voriconazole in plasma. Background technique [0002] Tuberculosis is a chronic respiratory infectious disease caused by Mycobacterium tuberculosis. The prevention and treatment of tuberculosis mainly rely on long-term combined chemotherapy against Mycobacterium tuberculosis. First-line anti-tuberculosis drugs such as isoniazid, rifampicin, rifapentine, Ethambutol, pyrazinamide, etc. play a dominant role in the treatment of tuberculosis. In addition, the anti-tuberculosis activity of fluoroquinolone antibiotics has been paid more and more attention, and its representative drug levofloxacin has received good results in the treatment of tuberculosis. These anti-tuberculosis drugs are concentration-dependent a...

Claims

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Application Information

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IPC IPC(8): G01N30/02G01N30/06G01N30/72G01N30/86
CPCG01N30/02G01N30/06G01N30/72G01N30/8634G01N2030/045
Inventor 赵冠人陈明车玲彭明丽孟瑾吴漫
Owner 中国人民解放军总医院第八医学中心
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