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Method for quantitative detection of S configuration Rivaroxaban and R configuration Rivaroxaban drug concentration in mice by LC-MS

A technology for quantitative detection of rivaroxaban, which is applied in the field of medical testing, can solve the problems of no determination of racemate administration, no change of rivaroxaban samples, etc., and achieve the effect of lowering the detection limit

Active Publication Date: 2015-01-28
上海柏狮生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] At present, what is reported in the existing literature is mainly the determination of the content of rivaroxaban in Chinese patent medicine preparations by reverse-phase high-performance liquid chromatography (HPLC); The plasma concentration of rivaroxaban was used to calculate the pharmacokinetic parameters of rivaroxaban after intravenous injection. However, this method only used a common C18 column to analyze the single configuration drug of rivaroxaban, and did not measure the administration of the racemate. Therefore it is not possible to say whether the rivaroxaban samples were altered in mice

Method used

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  • Method for quantitative detection of S configuration Rivaroxaban and R configuration Rivaroxaban drug concentration in mice by LC-MS
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  • Method for quantitative detection of S configuration Rivaroxaban and R configuration Rivaroxaban drug concentration in mice by LC-MS

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1 Determination of detection method

[0038] 1.1 Experimental equipment and reagents

[0039] instrument:

[0040] The liquid chromatograph is Waters ACQUITY UPLC (Waters Company), equipped with Binary Solvent Manager, Column, PDA detector; chromatographic column: CHIRALPAK IC (4.6mmΦ*250cm 5μm) (Daicel (China) Investment Co., Ltd.);

[0041] The mass spectrometer is Quattro Premier XE (Waters Company), equipped with electrospray ionization ion source ESI and atmospheric pressure chemical ionization source (APCI), Masslynx V4.1 workstation, Ultra Sonic Cleaner USK Type ultrasonic cleaner;

[0042] FA604A electronic balance (Shanghai Ketian Electronic Instrument Co., Ltd.);

[0043] Vortex Mixer XW-80A (Haimen Qilinbeier Instrument Manufacturing Co., Ltd.)

[0044] TGL-16G high-speed desktop centrifuge (Shanghai Anting Scientific Instrument Factory)

[0045] DC-12 nitrogen blowing instrument (Shanghai Anpu Scientific Instrument Co., Ltd.)

[0046] Pipe...

Embodiment 2

[0074] Example 2 Methodology verification experiment

[0075] 2.1 Linearity and correlation coefficients of the method

[0076] Dilute the standard stock solution of 100 μg / mL rivaroxaban racemate (composed of 50% each of S-configuration rivaroxaban and R-configuration rivaroxaban) with acetonitrile to a concentration of 0.01 μg / mL, 0.05μg / mL, 0.10μg / mL, 0.50μg / mL, 1.00μg / mL, 5.00μg / mL, 10.00μg / mL rivaroxaban racemate standard sample solution;

[0077] Perform liquid mass analysis according to "1.2 Liquid phase conditions" and "1.3 Mass spectrometry conditions" in Example 1, and obtain the ion current intensity of the ion pair 436.0 / 144.9 in the multiple reaction monitoring mode;

[0078] A standard linear regression equation is made with the sample concentration of S-configuration rivaroxaban as the abscissa, and the peak area of ​​the measured ion current intensity as the ordinate. The linear equation of the obtained S-configuration rivaroxaban sample was y=32506.58x...

Embodiment 3

[0090] Example 3 Determination of actual samples

[0091] 3.1. Plasma sample preparation

[0092] When administering, the solvent for dissolving the rivaroxaban drug is a mixed solution of ethanol: polyethylene glycol 400: water with a volume ratio of 20:60:20;

[0093] Weigh 10.37 mg of S-configuration rivaroxaban, dissolve it with 10.37 mL of the above mixed solution, and prepare a sample administration solution of S-configuration rivaroxaban with a concentration of 1.0 mg / mL;

[0094] In addition, 9.886 mg of S-configuration rivaroxaban and 9.991 mg of R-configuration rivaroxaban were weighed and mixed together in a sample bottle, and 9.9 mL of the above mixed solution was ultrasonically dissolved to prepare a concentration of 1.0 mg / mL A sample dosing solution of the rivaroxaban racemate.

[0095] Administer mice at a dose of 10.0 mg per kilogram of mice;

[0096]The S-configuration rivaroxaban sample administration solution with a concentration of 1.0mg / mL was ad...

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Abstract

The invention discloses a method for quantitative detection of S configuration Rivaroxaban and R configuration Rivaroxaban drug concentration in a mice by LC-MS (Liquid Chromatography-Mass Spectrometry).The method comprises the following steps: pretreating a mice plasma sample, analyzing the pretreated mice plasma sample by liquid chromatography and mass spectrometry sequentially in a combined manner, finally quantifying through an external standard method, and using a peak area to calculate the S configuration Rivaroxaban and R configuration Rivaroxaban drug concentration in plasma. According to the method for quantitative detection of S configuration Rivaroxaban and R configuration Rivaroxaban drug concentration in the mice by LC-MS, the chiral separation time is shortened, and the analysis time is only 13 min. The method has the detection limit of 3 ng / mL, the quantitative limit of 10 ng / mL, a good linear relation within the range of 0.01-10 micrograms per millimeter, the recovery rate of 86-112%, the intra-day RSD (Relative Standard Deviation) of 5.50-8.86%, and the inter-day RSD of 8.39-17.6%; the detection and analysis requirements for S configuration Rivaroxaban and R configuration Rivaroxaban drug concentration in the mice are met.

Description

technical field [0001] The invention belongs to the technical field of medical detection, and relates to a method for detecting the content of the S-configuration of rivaroxaban drug and its isomer R-configuration in plasma, and specifically relates to the quantitative detection of the S-configuration in mice by liquid mass spectrometry The method of concentration of rivaroxaban and R-configuration rivaroxaban. Background technique [0002] Rivaroxaban is a new oral anticoagulant drug, which is a highly selective and competitive drug that directly inhibits factor Xa in the free state, and can also inhibit the activity of factor Xa in the bound state and prothrombin. Platelet aggregation has no direct effect. It has the characteristics of high bioavailability, broad disease spectrum for treatment, stable dose-effect relationship, convenient oral administration and low bleeding risk. Rivaroxaban (rivaroxaban, BAY5927939, trade name: Xarelto) chemical name: 5-chloro-N-{[2-oxo...

Claims

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Application Information

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IPC IPC(8): G01N30/88G01N30/06
Inventor 潘仙华闫茜张瑞敏于一文徐娜许旭陈思羽
Owner 上海柏狮生物科技有限公司