Method for detecting furosemide in human plasma by liquid chromatography-mass spectrometry and application thereof

Abstract

The invention relates to a method for detecting furosemide in human plasma by liquid chromatography-mass spectrometry and application thereof, belonging to the field of biological analysis. The methodadopts a protein precipitation pretreatment method using a deuterated internal standard substance as a precipitating agent, adopts Inertsil C8-3 column isocratic elution, and adopts ESI (ElectroSprayIonization) tandem mass spectrometry detection. Through adoption of the method of the invention, the furosemide has a good linear range of 7.5-1500ng / mL, the furosemide matrix effect factor is 107%,the plasma matrix does not influence the accurate quantification of furosemide, and the extraction recovery rate is 99.2%. The method has the advantages of strong specificity and selectivity, high sensitivity, rapid detection and small dosage, and capacity for meeting the requirements of simple, reliable, high-flux and condition-controllable clinical mass sample analysis. The method of the invention can be used for evaluating the bio-equivalence of each formulation of furosemide.

Description

technical field [0001] The invention belongs to the technical field of biological analysis, and in particular relates to a method for quantitatively detecting furosemide concentration in blood plasma by liquid mass spectrometry and an application thereof. Background technique [0002] Furosemide is mainly used for the treatment of edema caused by congestive heart failure, liver cirrhosis and kidney disease, etc. － and Na + It works by absorbing it, and its plasma protein binding rate is about 97%. There are significant intra-individual and inter-individual differences in the bioavailability of furosemide, which belongs to the highly variable class of drugs. At present, there are few reports on the pharmacokinetics of furosemide, and the studies in the Chinese population are even more limited. The chemical structure of furosemide is shown below: [0003] [0004] Markus established a liquid-liquid extraction liquid phase detection method in 2013, using 0.5 mL of plasma...

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Problems solved by technology

[0004] Markus established a liquid-liquid extraction liquid phase detection method in 2013, using 0.5 mL of plasma, which is not suitable for large-scale sample detection, using a fluorescence detector, and the selectivity is poor. The liquid-liquid extraction method is used for pretreatment. It needs to be reconstituted after drying with nitrogen, which is complicated and time-consuming

[0005] In 2013, Xiaomin Yang established a liquid-liquid extraction LC-MS method and initially applied it to the blood concentration of patients with clinical renal failure. The extraction method has many steps and takes a long time

The lower limit of quantitation was 12.8 ng / mL, and its pharmacokinetic characteristics could not be fully detected

[0006] Zeng Jing established a protein precipitation liquid mass spectrometry method in 2016 to evaluate the bioequivalence of furosemide tablets in Chinese healthy subjects. Although this method has a low lower limit of quantitation and a wide linear range, the plasma dosage of 0.2 mL is more And the sample processing process is complicated, not suitable for large-scale sample processing

This method uses nimesulide as an internal standard, which is not suitable for mass spectrometry detection, and the chromatographic run time is about 4.7min, which is not suitable for large-scale sample detection

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