[go: up one dir, main page]

WO2011097933A1 - Kit pour détecter le 3-sulfate de glycochénodésoxycholate et le glycochénodésoxycholate dans du sang - Google Patents

Kit pour détecter le 3-sulfate de glycochénodésoxycholate et le glycochénodésoxycholate dans du sang Download PDF

Info

Publication number
WO2011097933A1
WO2011097933A1 PCT/CN2010/080483 CN2010080483W WO2011097933A1 WO 2011097933 A1 WO2011097933 A1 WO 2011097933A1 CN 2010080483 W CN2010080483 W CN 2010080483W WO 2011097933 A1 WO2011097933 A1 WO 2011097933A1
Authority
WO
WIPO (PCT)
Prior art keywords
gcdcs
acid
liver cancer
afp
kit
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2010/080483
Other languages
English (en)
Chinese (zh)
Inventor
王文昭
谈冶雄
尹佩源
洪毅
路鑫
汤靓
王红阳
许国旺
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dalian Institute of Chemical Physics of CAS
Second Military Medical University SMMU
Original Assignee
Dalian Institute of Chemical Physics of CAS
Second Military Medical University SMMU
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dalian Institute of Chemical Physics of CAS, Second Military Medical University SMMU filed Critical Dalian Institute of Chemical Physics of CAS
Publication of WO2011097933A1 publication Critical patent/WO2011097933A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/94—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
    • G01N2030/8813—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/72—Mass spectrometers
    • G01N30/7233—Mass spectrometers interfaced to liquid or supercritical fluid chromatograph

Definitions

  • the invention relates to the field of analytical chemistry and medicine, and is an ultra performance liquid chromatography mass spectrometry method for detecting human blood based on a kit for detecting blood 3-glycine chenodeoxycholic acid and glycine chenodeoxycholic acid (GCDCS and GCDCA).
  • GCDCS and GCDCA 3-glycine chenodeoxycholic acid and glycine chenodeoxycholic acid
  • Liver cancer is one of the common malignant tumors in China. Liver cancer either originates from the liver itself or is derived from the metastatic effects of other cancer cells in the body.
  • Primary liver cancer refers to a malignant tumor of liver cells or intrahepatic cholangiocarcinoma cells, and the incidence of primary liver cancer from the liver has been the first in liver malignant tumors. It ranks third only to gastric cancer and esophageal cancer in malignant tumor mortality, and second in rural areas in some areas, second only to gastric cancer. China has died of about 110,000 liver cancers per year, accounting for 45% of the world's liver cancer deaths. In recent years, the incidence and mortality of primary liver cancer in China have increased, while in rural areas it is significantly higher than in urban areas.
  • liver cancer is mainly associated with diseases such as hepatitis B, hepatitis C virus infection and cirrhosis.
  • the early symptoms of liver cancer are often not obvious. Most patients are asymptomatic, and the physical examination lacks the signs of the tumor itself. This period is called the sub-clinical stage. Once the symptoms of liver cancer appear, it means that most of the patients have entered the middle and late stages.
  • General imaging examinations and physical examinations have limited effects. They are often found and confirmed in the middle and late stages, and lack of early warning value.
  • liver cancer serum marker is alpha-fetoprotein (AFP).
  • AFP alpha-fetoprotein
  • serum levels have the disadvantage of being less sensitive and less specific in the diagnosis of liver cancer, and the detection rate when used alone in diagnosis is generally only about 50%-75%. Therefore, in order to improve the sensitivity and specificity of clinical diagnosis, it is imperative to develop new detection methods.
  • Bile acid is directly synthesized from cholesterol in the mitochondria of the liver parenchyma cells. It is concentrated in the gallbladder after transport through the bile duct. It is a general term for a large class of choline acids present in bile. As a major product of cholesterol metabolism, bile acids have similar sterol core structures and branched structures of different combinations.
  • the human body mainly contains 5 kinds of free bile acids and 10 kinds of bound bile acids which are combined with glycine and taurine; meanwhile, the human body also contains a small amount of monosulfated bile acids combined with 3 hydroxyl groups.
  • Bile acid has been considered to only promote the digestion and absorption of lipids, maintain the dynamic balance of bile acid secretion, inhibit the precipitation of cholesterol in bile to form gallstones, and assist in the diagnosis of diseases such as viral hepatitis and biliary obstruction. .
  • liver parenchyma cells When the human body suffers from hepatobiliary diseases, especially malignant tumors, the metabolism of the liver's basic unit, the liver parenchyma cells, will be stimulated by cancer to change the metabolism of bile acids.
  • serum total bile acid (TBA) content has been widely used in the auxiliary diagnosis of chronic diseases such as viral hepatitis and cirrhosis, its role in the diagnosis of liver cancer is extremely small. And because the serum total bile acid content is determined based on the 3 hydroxysterol method, it does not reflect the changes in the body's bile acids when the body suffers from primary liver cancer. In view of this, measuring the changes in the content of bile acids in the blood is beneficial to us to understand the metabolic changes of hepatocytes in order to find effective potential markers to develop and establish new methods for detecting liver cancer.
  • Document 12 Makino, I.; Shinozak.K; Nakagawa, S.; Mashimo , K. Journal of Lipid Research 1974, 15, 132-138. ); Conventional liquid chromatography techniques have shortcomings such as low detection sensitivity or complex derivatization processes (Document 11: Roda, A.; Piazza, F.; Baraldini, M . Journal of Chr Omatography B-Analytical Technologies in the Biomedical and Life Sciences 1998, 717, 263-278. Document 13: Sakakura, H.; Kimura, N.; Takeda, H.; Komatsu, H.; Ishizaki, K.; Nagata, S Journal of Chromatography B 1998, 718, 33-40. ).
  • Document 16 Tagliacozzi, D.; Mozzi, A. R; Casetta, B.; Bertucci, P.; Bernardini, S.; Di Ilio, C; Urbani, A.; Federici, G. Clinical Chemistry and Laboratory Medicine 2003, 41, 1633-1641.
  • Document 17 Ye, L.; Liu, S. Y; Wang, M.; Shao, Y; Ding, M. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences 2007, 860, 10-17.
  • Document 18 Ando, M.; Kaneko, T.
  • the multi-step SPE column is used to separate the sulfide bile acid, and has a large ion suppression effect and low resolution, and can only be used for detecting monosulfation.
  • Disadvantages such as bile acid see references: Ikegawa S, Yanagihara T, Murao N, etc. JOURNAL OF MASS SPECTROMETRY. 1997, 32, 401-407.).
  • bile acid see references: Ikegawa S, Yanagihara T, Murao N, etc. JOURNAL OF MASS SPECTROMETRY. 1997, 32, 401-407.
  • the invention provides a kit for rapidly detecting blood 3-glycystase chenodeoxycholic acid and glyco-eodeoxycholic acid.
  • the kit does not require complicated SPE pretreatment process, and not only detects blood 3-sulfuric acid.
  • Glycine chenodeoxycholic acid/time flux is high, and it has the characteristics of low detection cost, good repeatability and high stability. Summary of the invention
  • the object of the present invention is to develop a kit for detecting 3-glycine chenodeoxycholic acid and glycine chenodeoxycholic acid in blood.
  • the method for detecting 3-glycylic acid chenodeoxycholic acid and glycine chenodeoxycholic acid in the blood sample has the characteristics of low detection cost, good repeatability, high stability, fast and high efficiency; only one 19 is needed for determining an actual sample. Minutes, suitable for clinical applications.
  • the kit consists of three parts: (1) an internal standard, an isoleucine phenanthride or a bile acid isotope standard; (2) a buffer of ammonium acetate, ammonium formate or ammonium hydrogencarbonate at a pH of 4.0 to 8.0; 3) Eluent - acetonitrile or methanol.
  • This kit uses isoleucine phenanthroline as an internal standard, which can reduce the analysis cost and enhance the detection accuracy.
  • the pH of 5.0 buffer ammonium acetate, ammonium formate or ammonium bicarbonate, eluent acetonitrile system can be obtained.
  • the present invention has also been developed based on the use conditions of the test kit and has been applied in normal control, hepatitis, cirrhosis and liver cancer samples.
  • Kit use conditions The chromatographic instrument is Waters ultra-high performance liquid chromatography, the column is C8 column, the column temperature is 60 degrees Celsius, the flow rate is 0.5 ml/min (C18 column can also be selected, the column temperature is 25-60 degrees Celsius, the flow rate is 0.2. -1.
  • GCDCS was significantly elevated in the liver cancer group compared with the normal group.
  • the sensitivity of GCDCS for judging liver cancer was 75.56%, and the specificity was 88.89%.
  • the sensitivity of using AFP to judge liver cancer was 62.2% and the specificity was 100%.
  • 17 samples with AFP values less than 20 ug/L (false negative) were judged by GCDCS, and 14 of them were found to be greater than 0.21 (positive result), which can be judged as liver cancer. This indicates that GCDCS has good complementarity with AFP and can be used to assist AFP in primary hepatocellular carcinoma screening.
  • hepatitis GCDCS in the blood of the cirrhosis group was compared with normal controls and liver cancer groups, and GCDCS was found to be higher in hepatitis and cirrhosis.
  • the changes in the content of GCDCA in the normal control group, hepatitis, cirrhosis and liver cancer group were found to be similar to GCDCS.
  • its content in the liver cancer group was higher than that in the normal group but not significant.
  • GCDCS/GCDCA was significantly elevated in the liver cancer group compared to the three groups of non-hepatoma groups.
  • the method of the invention has the following effects:
  • the separation effect not only detects 15 kinds of conventional bile acids in the blood, but also can detect several sulfated bile acids such as 3-glycine chenodeoxycholic acid.
  • the method based on kit development has the following characteristics:
  • the sample collection and storage adopt standardized operation procedures to avoid introducing human error; the pretreatment process is simple, and the analysis process adopts high temperature and high speed method, which not only improves the separation of analytes.
  • the ability to resolve, and greatly shorten the analysis time, can separate the conventional bile acids, and can simultaneously separate several sulfated bile acids.
  • GCDCS/GCDCA can assist AFP in the diagnosis of primary liver cancer.
  • the method for diagnosing liver cancer established by this method has the characteristics of safety, reliability, high flux, high sensitivity and specificity, and is suitable for early screening and auxiliary diagnosis of liver cancer.
  • FIG. 1 TIC diagram of human serum bile acid: 1, leucine brain phenanthrene (internal standard); 2, 3-glycine ursodeoxycholic acid (GUDCS); 3, 3-glycolic acid chenodeoxycholic acid (GCDCS) 4, 3-glycylic acid deoxycholic acid (GDCS); 5, glycine ursodeoxycholic acid (GUDCA); 6, burdock chenodeoxycholic acid (TUDCA); 7, glycocholic acid (GCA); 8, burdock cholic acid (TCA); 9, glycine chenodeoxycholic acid (GCDCA); 10, burdock chenodeoxycholic acid (TCDCA); 11, glycodeoxycholic acid (GDCA); 12, burdock deoxygenation Cholic acid (TDCA); 13, cholic acid (CA); 14, ursodeoxycholic acid (UDCA); 15, glycocholic acid (GLCA); 16, burdock cholic acid (TLCA); 17, goose deoxygenation Cholic acid (
  • the sample was thawed at room temperature, and 150 ⁇ l of serum was added. 600 ⁇ l of acetonitrile and 30 ⁇ l of isoleucine phenanthride were added to a concentration of 3.3 ⁇ g/ml acetonitrile (acetonitrile water volume ratio of 1:1). After shaking for 30 seconds, centrifugation at 9000 g for 15 minutes at 4 °C, 650 ⁇ l of the supernatant was lyophilized, and the solution was mixed with acetonitrile in a volume ratio of 1:3, ⁇ ⁇ ⁇ reconstituted, and centrifuged at 9000 g at 4 ° C.
  • Mass spectrometry conditions are: Mass spectrometer is Waters single quadrupole mass spectrometer, detected by electrospray ion source negative ion mode; desolvation gas and cone gas flow are divided into 700 L/h and 50 L/h, desolvation gas and The cone gas is high purity nitrogen; the desolvation gas temperature is 300 V, the ion source temperature is 120 V; the capillary voltage and the cone voltage are 2800 V and 45 V, respectively; detection by selective ion monitoring mode: 0 ⁇ 2.6 min Detection of ions 528.3 and 554.3, 2.65 ⁇ 3.7 min detection of ions 448.3, 464.3, 498.3 and 514.3, 3.75 ⁇ 6 min detection ions 391.3, 407.3, 448.3 and 498.3, 6.05 ⁇ 19 min detection ions 375.3, 391.3, 432.3 and 482.3; per 0.1 Data is collected once in seconds ( Figure 1).
  • GCDCS in the blood of hepatitis and cirrhosis, its upstream metabolite GCDCA and its related parameters GCDCS/GCDCA were compared with normal controls and liver cancer groups.
  • GCDCS was found to be more abundant in hepatitis and cirrhosis (Fig. 2A).
  • GCDCS/GCDCA was significantly elevated in the liver cancer group compared to the three groups of non-hepatoma groups (Fig. 3A).
  • GCDCS/GCDCA By comparison, we found that the use of GCDCS/GCDCA to diagnose liver cancer not only has higher sensitivity and specificity, but only GCDCS/GCDCA and AFP are not significant, indicating that GCDCS/GCDCA has more potential for application, and its combined diagnosis with AFP is more Helps improve the ability to detect liver cancer. For example, when AFP was used to detect liver cancer, 17 of 45 patients with liver cancer had a negative reaction (AFP ⁇ 20 ng/L), and when the GCDCS/GCDCA method was used to diagnose these 17 patients, 10 of them were found to be present. Positive reaction (GCDCS/GCDCA>0.097). This indicates that GCDCS/GCDCA has good complementarity with AFP, and Table 2 shows the sensitivity and specificity of GCDCS, AFP, GCDCS/GCDCA, and "AFP+GCDCS/GCDCA".

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Food Science & Technology (AREA)
  • Biotechnology (AREA)
  • Analytical Chemistry (AREA)
  • Cell Biology (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)

Abstract

La présente invention concerne un kit pour détecter le 3-sulfate de glycochénodésoxycholate et le glycochénodésoxycholate dans du sang. Le kit est constitué d'un isotope standard de leucine-encéphaline (Lep) ou d'acide biliaire en tant qu'étalon interne, d'acétate d'ammonium ou de formiate d'ammonium ou de bicarbonate d'ammonium en tant que solution tampon ayant un pH de 4,0 à 8,0, et d'acétonitrile ou de méthanol en tant qu'éluant.
PCT/CN2010/080483 2010-02-10 2010-12-30 Kit pour détecter le 3-sulfate de glycochénodésoxycholate et le glycochénodésoxycholate dans du sang Ceased WO2011097933A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201010108382.1 2010-02-10
CN 201010108382 CN101995441A (zh) 2010-02-10 2010-02-10 检测血中3-硫酸甘氨鹅脱氧胆酸和甘氨鹅脱氧胆酸的试剂盒

Publications (1)

Publication Number Publication Date
WO2011097933A1 true WO2011097933A1 (fr) 2011-08-18

Family

ID=43785881

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2010/080483 Ceased WO2011097933A1 (fr) 2010-02-10 2010-12-30 Kit pour détecter le 3-sulfate de glycochénodésoxycholate et le glycochénodésoxycholate dans du sang

Country Status (2)

Country Link
CN (1) CN101995441A (fr)
WO (1) WO2011097933A1 (fr)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102798672A (zh) * 2011-05-21 2012-11-28 中国科学院大连化学物理研究所 一种检测血中gcdcs和gcdca的试剂盒
CN103782166B (zh) * 2011-06-06 2018-01-16 沃特世科技公司 用于定量样品中目标分析物的组合物、方法和试剂盒
CN107621503A (zh) * 2016-07-14 2018-01-23 上海可力梅塔生物医药科技有限公司 胆汁和血清中熊脱氧胆酸的纯化分离和lc‑ms/ms检测
CN107621502A (zh) * 2016-07-14 2018-01-23 上海可力梅塔生物医药科技有限公司 基于lc‑ms/ms的胆汁和血清中16种胆汁酸的定量
CN108072704B (zh) * 2016-11-08 2021-05-11 中国科学院大连化学物理研究所 基于液相色谱质谱联用的粪便中胆汁酸的检测方法
CN107356694A (zh) * 2017-07-21 2017-11-17 杭州汉库医学检验所有限公司 一种高效检测血液中15种胆汁酸的方法
CN107656007A (zh) * 2017-09-21 2018-02-02 杭州汉库医学检验所有限公司 组合型血清代谢标志物在制备用于诊断肝病发展进程试剂盒的用途、试剂盒及其筛选方法
CN107843671A (zh) * 2017-12-21 2018-03-27 杭州佰勤医疗器械有限公司 一种高通量液相色谱串联质谱的高通量液相色谱串联质谱的检测方法
CN109030676A (zh) * 2018-07-06 2018-12-18 易达精准（杭州）科技有限公司 同时测定16种胆汁酸的串联质谱检测试剂盒及其应用
CN113009061A (zh) * 2021-03-02 2021-06-22 广东南芯医疗科技有限公司 一种同时检测血液样品中多种胆汁酸的方法及试剂盒
CN114235995A (zh) * 2021-12-03 2022-03-25 天津国科医工科技发展有限公司 检测血清中15种胆汁酸的方法
CN115128257B (zh) * 2022-07-06 2025-02-18 南京医科大学 肝癌发病风险预测的代谢标志物及其应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990011526A1 (fr) * 1988-11-01 1990-10-04 Enzymatix Ltd. Diagnostic de cancer
CN1608138A (zh) * 2001-12-21 2005-04-20 艾蒂尔药物有限公司 检测碱性鞘磷脂酶的分析方法以及用于该方法的试剂盒

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1308679C (zh) * 2004-01-14 2007-04-04 江苏康缘药业股份有限公司 一种治疗小儿肺热咳嗽口服液的质量检测方法
CN1261762C (zh) * 2004-08-16 2006-06-28 江苏中康药物科技有限公司 一种体外培植牛黄的质量鉴别方法
WO2008006006A1 (fr) * 2006-07-03 2008-01-10 Beth Israel Deaconess Medical Center, Inc. Procédés histologiques

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990011526A1 (fr) * 1988-11-01 1990-10-04 Enzymatix Ltd. Diagnostic de cancer
CN1608138A (zh) * 2001-12-21 2005-04-20 艾蒂尔药物有限公司 检测碱性鞘磷脂酶的分析方法以及用于该方法的试剂盒

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SWOBODNIK, W.: "Analysis of Conjugated Bile Acids in Human Serum by High- Performance Liquid Chromatography Using Post-Column Enzyme Reaction and Off-Line Fluorimetric Determination.", JOURNAL OF CHROMATOGRAPHY ., no. 423, 1987, pages 75 - 84 *

Also Published As

Publication number Publication date
CN101995441A (zh) 2011-03-30

Similar Documents

Publication Publication Date Title
WO2011097933A1 (fr) Kit pour détecter le 3-sulfate de glycochénodésoxycholate et le glycochénodésoxycholate dans du sang
CN105738626B (zh) 一种新的血清代谢物的组合及其作为肝癌诊断标志物的用途
JP5737761B2 (ja) 肝細胞癌マーカー
JP2016197110A (ja) 質量分析によってジヒドロキシビタミンｄ代謝物を検出するための方法
WO2012000770A1 (fr) Méthodes de diagnostic des maladies du foie
US10502748B2 (en) Method of differentiating stable angina pectoris from acute coronary syndrome and diagnostic kit thereof
Guan et al. Simultaneous metabolomics and proteomics analysis of plasma-derived extracellular vesicles
Hou et al. Studies on the interactions between ginsenosides and liposome by equilibrium dialysis combined with ultrahigh performance liquid chromatography-tandem mass spectrometry
US20240319211A1 (en) Content conversion method of free components by transforming ultrafiltration to equilibrium dialysis
Uzzaman et al. Discovery of small extracellular vesicle proteins from human serum for liver cirrhosis and liver cancer
CN103884782B (zh) 基于液相色谱-质谱联用的大规模血浆鞘脂轮廓分析方法
Xu et al. Fast and quantitative determination of saxitoxin and neosaxitoxin in urine by ultra performance liquid chromatography-triple quadrupole mass spectrometry based on the cleanup of solid phase extraction with hydrophilic interaction mechanism
CN103235050A (zh) 三七总皂苷注射剂的质量控制方法
Peake et al. Improved separation and analysis of plasma amino acids by modification of the MassTrak™ AAA Solution Ultraperformance® liquid chromatography method
KR101946884B1 (ko) 대사체 분석을 이용한 베체트병의 진단방법
Han et al. Serum metabolic profiling of rats infected with Clonorchis sinensis using LC-MS/MS method
RU2702998C1 (ru) Способ контроля содержания противотуберкулёзных препаратов основного ряда и их токсичных метаболитов в плазме крови
Amir Hamzah et al. Advances in targeted liquid chromatography‐tandem mass spectrometry methods for endocannabinoid and N‐acylethanolamine quantification in biological matrices: A systematic review
Wang et al. Simultaneous determination of three biomarkers of non-small cells lung cancer in urine by pipette-tip solid-phase extraction coupled with liquid chromatography tandem mass spectrometry
CN103604875A (zh) 甲基苯丙胺滥用者血清代谢标志物的测定方法
CN113138274A (zh) 一种组合物和应用及肺癌患者诊断试剂盒
CN102565267B (zh) 筛查结直肠癌的试剂盒
CN118243826B (zh) 一种用于评估新生儿胆道闭锁风险的代谢物组合及其应用
CN102798672A (zh) 一种检测血中gcdcs和gcdca的试剂盒
Fang et al. Determination of tetrodotoxin in human plasma and urine using online MCX SPE column cleanup coupled with liquid chromatography-tandem mass spectrometry

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10845603

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 10845603

Country of ref document: EP

Kind code of ref document: A1