WO2012020985A2 - Method for analyzing aspirin in plasma with liquid chromatography-mass spectrometry - Google Patents
Method for analyzing aspirin in plasma with liquid chromatography-mass spectrometry Download PDFInfo
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- WO2012020985A2 WO2012020985A2 PCT/KR2011/005843 KR2011005843W WO2012020985A2 WO 2012020985 A2 WO2012020985 A2 WO 2012020985A2 KR 2011005843 W KR2011005843 W KR 2011005843W WO 2012020985 A2 WO2012020985 A2 WO 2012020985A2
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- plasma
- liquid chromatography
- asa
- aspirin
- mass spectrometry
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- 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
-
- 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
- G01N2030/009—Extraction
-
- 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
- G01N2030/884—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 organic compounds
Definitions
- the present invention relates to a method for analyzing aspirin in plasma with liquid chromatography-mass spectrometry.
- Acetylsalicylic acid (ASA, aspirin) has been widely used as an analgesic, anti-inflammatory, antipyretic and antithrombotic drug.
- ASA is rapidly hydrolyzed in vivo to produce salicylic acid (SA) responsible for the pharmacological activity. Therefore, in order to analyze the amounts of ASA, it is required to determine SA level in blood with liquid chromatography-mass spectrometry (LC-MS).
- SA salicylic acid
- ASA high performance liquid chromatography
- protic solvents such as water or methanol
- plasma protic solvents
- ASA in water has the best stability when pH is 2-3, and at pH 7 about 20% of ASA is degraded to SA within a day.
- the half-life of ASA is about one hour in plasma at 37 ° C , the partial degradation of ASA may occur after sampling and before injecting it into the HPLC system.
- a part of SA may be lost by sublimation during sample treatment comprising evaporation step. Therefore, there was a difficulty in determining the accurate amount of ASA by employing HPLC.
- Frieder Kees et al disclose a method for analyzing ASA by way of acidifying a sample to adjust its pH in the range of 2 to 3, cooling and storing at -70 °C before use, in order to prevent the degradation of ASA in plasma (Frieder ees et al., Journal of Chromatography B, 677, 172-177 (1996)).
- Bouche et al disclose a method for analyzing ASA with ESI(-)- LC-MS/MS (M.P. Bouche et al., Combining selectivity from chromatography and fast ion separation by MS in bioanalysis).
- the method has a long analyzing time, a tailing phenomenon and poor stability due to high pH.
- the method was not suitable for quantification of human plasma, since the limit of quantification (LOQ) of ASA and SA represents 80 ng/ml and 60 ng/ml, respectively, which means low sensitivity.
- LOQ limit of quantification
- Soo yung Bae et al and Xiangrong et al disclose methods for analyzing ASA by extraction using a mixture of acetonitrile and aqueous 0.1% formic acid in a ratio of 80 : 20 (v/v (%)) and 63 : 37 (v/v (%)), respectively, as a mobile phase.
- both methods fail to completely isolate ASA (Soo Kyung Bae et al, Biomed. chromatogram., 22: 590-595 (2008)); and (Xiangrong et al., Biomed. chromatogram., 23: 973-979 (2009)).
- the present inventors have endeavored to determine the accurate levels of ASA and SA in plasma, and found a stable and easy method for analyzing ASA and SA in plasma with liquid chromatography-mass spectrometry.
- ASA aspirin
- a method for analyzing aspirin in plasma with liquid chromatography- mass spectrometry which comprises the steps of:
- step 3 subjecting the resulting mixture obtained in step 2) to liquid chromatography-mass spectrometry for a quantitative analysis of aspirin in plasma.
- Figs. 1 to 3 MS/MS spectrum results of aspirin, salicylic acid and ibuprofen, respectively.
- Fig. 4 liquid chromatography results for 250 ng/ml of aspirin, 78.125 ng/ml of salicylic acid, and 500 ng/ml of ibuprofen (ISTD).
- the present invention provides a method for analyzing aspirin in plasma with liquid chromatography-mass spectrometry which comprises the steps of: 1) adding an internal standard material and extracting solvent to a plasma sample, centrifuging the sample, and collecting a supernatant therefrom; 2) concentrating and dissolving the supernatant in acetonitrile; and 3) subjecting the resulting mixture obtained in step 2) to liquid chromatography-mass spectrometry for a quantitative analysis of aspirin in plasma.
- step 1) of the present invention an internal standard material and extracting solvent is added to a plasma sample, and the sample is centrifuged to collect a supernatant.
- the internal standard material may be ibuprofen
- the extracting solvent may be methyl tert-butyl ether (MTBE) containing 0.5% acetic acid.
- ASA in plasma has the best stability when pH is 2 to 3, and therefore, MTBE containing 0.5% acetic acid used as the extracting solvent is useful in maintaining a certain pH level, thereby achieving the stability of ASA.
- the supernatant may be dried and concentrated.
- the dried concentrates may be dissolved in acetonitrile.
- the dried concentrates may be dissolved in 50% acetonitrile.
- the resulting mixture obtained in step 2) may be subjected to liquid chromatography-mass spectrometry for a quantitative analysis of aspirin in plasma.
- the plasma sample obtained in step 2) may be introduced to the liquid chromatography (LC) column, and mass spectrophotometer (MS).
- MS mass spectrophotometer
- the plasma sample applied to MS may be ionized and quantified for analyzing the amount of ASA in plasma.
- a mobile phase used in LC may be a mixture of acetonitrile and formic acid, preferably, a mixture of acetonitrile and 0.01% formic acid in a ratio ranging from 65 : 35 to 75 : 25 (v/v (%)), preferably, 70 : 30 (v/v (%)).
- the plasma sample may be ionized in a negative ionization mode, and quantified in a multiple reaction monitoring (MRM) mode.
- MRM multiple reaction monitoring
- MRM mode are shown in Figs. 1 to 3, respectively.
- MS/MS spectrum of ASA quantified in MRM mode represents that Ql is about 179 (m/z), and Q3 is about 137 and 93 (m/z).
- MS/MS spectrum of SA quantified in MRM mode shows that Ql is about 137 (m/z), and Q3 is about 93 and 65 (m/z).
- MS/MS spectrum of ibuprofen quantified in MRM mode demonstrates that Ql is about 205 (m/z), and Q3 is about 161 (m/z).
- Example 1 Construction of calibration curves
- Standard samples of ASA and SA were prepared by sequentially diluting standard solutions of 100 ⁇ g/mL of ASA and 1 mg/mL of SA with a dog's blank plasma, respectively, giving final concentrations of 2 to 1 ,000 ng/mL for ASA and 20 to 10,000 ng/mL for SA. 20 ⁇ , of the standard samples of different concentration levels were taken to each test tube with a cap. 50 iL of internal standard material (ibuprofen 500 ng/mL) was added to the test tube followed by adding 1 mL of methyl tert-butyl ether containing 0.5% acetic acid thereto. The mixture was centrifuged at 1 ,400 rpm for 10 min.
- Calibration curves were constructed based on the ratio of peak areas for ASA and SA to those for the internal standard material, and calculated by a weighted (1/x) least squares regression.
- LC chromatograms for 250 ng/ml of ASA, and 78.125 ng/ml of SA are shown in Fig. 4.
- Example 2 Sample analysis A blood sample was collected from a dog administered with aspirin, and stored at -70 ° C . The sample was thawed at room temperature, well mixed in a desktop mixer for 0.5 min. 20 ⁇ , of the resulting sample was transferred into a test tube with a cap. 50 ⁇ . of the internal standard material (ibuprofen 500 ng/mL) was added to the test tube followed by adding 1 mL of methyl tert-butyl ether containing 0.5% acetic acid thereto. The mixture was centrifuged at 1,400 rpm for 10 min. A supernatant was collected, and then dried and concentrated at 35 ° C using a vacuum dryer. The dried concentrates were dissolved in 500 ⁇ L of 50% acetonitrile and subjected to the LC-MS according to the procedure described in Example 1. Quantification of ASA and SA in plasma was performed using the calibration curves constructed in Example 1.
- the method for analyzing aspirin in plasma with LC-MS according to the present invention can stably and easily analyze ASA and S A without loss of their amounts even after sampling.
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Abstract
The present invention relates to a method for analyzing aspirin in plasma with liquid chromatography-mass spectrometry, which can stably and easily analyze ASA and SA without loss of their amounts even after sampling.
Description
DESCRIPTION
METHOD FOR ANALYZING ASPIRIN IN PLASMA WITH LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY
FIELD OF THE INVENTION
The present invention relates to a method for analyzing aspirin in plasma with liquid chromatography-mass spectrometry.
BACKGROUND OF THE INVENTION
Acetylsalicylic acid (ASA, aspirin) has been widely used as an analgesic, anti-inflammatory, antipyretic and antithrombotic drug. ASA is rapidly hydrolyzed in vivo to produce salicylic acid (SA) responsible for the pharmacological activity. Therefore, in order to analyze the amounts of ASA, it is required to determine SA level in blood with liquid chromatography-mass spectrometry (LC-MS).
However, two problems are associated with the high performance liquid chromatography (HPLC) analysis of ASA and SA in biological fluids. Firstly, ASA hydrolyzes to SA in protic solvents such as water or methanol, and also in plasma. ASA in water has the best stability when pH is 2-3, and at pH 7 about 20% of ASA is degraded to SA within a day. Also, since the half-life of ASA is about one hour in plasma at 37°C , the partial degradation of ASA may occur after sampling and before injecting it into the HPLC system. Secondly, a part of SA may be lost by sublimation during sample treatment comprising evaporation step. Therefore, there was a difficulty in determining the accurate amount of ASA by employing HPLC.
Accordingly, a number of methods have been reported for the analysis of ASA to solve these problems.
Frieder Kees et al disclose a method for analyzing ASA by way of
acidifying a sample to adjust its pH in the range of 2 to 3, cooling and storing at -70 °C before use, in order to prevent the degradation of ASA in plasma (Frieder ees et al., Journal of Chromatography B, 677, 172-177 (1996)).
Also, Bouche et al disclose a method for analyzing ASA with ESI(-)- LC-MS/MS (M.P. Bouche et al., Combining selectivity from chromatography and fast ion separation by MS in bioanalysis). However, the method has a long analyzing time, a tailing phenomenon and poor stability due to high pH. Also, the method was not suitable for quantification of human plasma, since the limit of quantification (LOQ) of ASA and SA represents 80 ng/ml and 60 ng/ml, respectively, which means low sensitivity.
Further, Soo yung Bae et al and Xiangrong et al disclose methods for analyzing ASA by extraction using a mixture of acetonitrile and aqueous 0.1% formic acid in a ratio of 80 : 20 (v/v (%)) and 63 : 37 (v/v (%)), respectively, as a mobile phase. However, both methods fail to completely isolate ASA (Soo Kyung Bae et al, Biomed. chromatogram., 22: 590-595 (2008)); and (Xiangrong et al., Biomed. chromatogram., 23: 973-979 (2009)).
Therefore, the present inventors have endeavored to determine the accurate levels of ASA and SA in plasma, and found a stable and easy method for analyzing ASA and SA in plasma with liquid chromatography-mass spectrometry.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the present invention to provide a method for analyzing aspirin (ASA) in plasma with liquid chromatography- mass spectrometry.
In accordance with one aspect of the present invention, there is provided a method for analyzing aspirin in plasma with liquid chromatography- mass spectrometry which comprises the steps of:
1) adding an internal standard material and extracting solvent to a plasma sample, centrifuging the sample, and collecting a supernatant
therefrom;
2) concentrating and dissolving the supernatant in acetonitrile; and
3) subjecting the resulting mixture obtained in step 2) to liquid chromatography-mass spectrometry for a quantitative analysis of aspirin in plasma.
BRIEF DESCRIPTION OF THE DRAWINGS
The above and other objects and features of the present invention will become apparent from the following description of the invention, when taken in conjunction with the accompanying drawings, which respectively show:
Figs. 1 to 3: MS/MS spectrum results of aspirin, salicylic acid and ibuprofen, respectively; and
Fig. 4: liquid chromatography results for 250 ng/ml of aspirin, 78.125 ng/ml of salicylic acid, and 500 ng/ml of ibuprofen (ISTD).
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a method for analyzing aspirin in plasma with liquid chromatography-mass spectrometry which comprises the steps of: 1) adding an internal standard material and extracting solvent to a plasma sample, centrifuging the sample, and collecting a supernatant therefrom; 2) concentrating and dissolving the supernatant in acetonitrile; and 3) subjecting the resulting mixture obtained in step 2) to liquid chromatography-mass spectrometry for a quantitative analysis of aspirin in plasma.
In step 1) of the present invention, an internal standard material and extracting solvent is added to a plasma sample, and the sample is centrifuged to collect a supernatant. In one embodiment of the present invention, the internal standard material may be ibuprofen, and the extracting solvent may be methyl tert-butyl ether (MTBE) containing 0.5% acetic acid. ASA in plasma has the best stability when pH is 2 to 3, and therefore, MTBE containing 0.5% acetic
acid used as the extracting solvent is useful in maintaining a certain pH level, thereby achieving the stability of ASA.
In step 2) of the present invention, the supernatant may be dried and concentrated. The dried concentrates may be dissolved in acetonitrile. In one embodiment of the present invention, the dried concentrates may be dissolved in 50% acetonitrile.
In step 3) of the present invention, the resulting mixture obtained in step 2) may be subjected to liquid chromatography-mass spectrometry for a quantitative analysis of aspirin in plasma. In one embodiment of the present invention, the plasma sample obtained in step 2) may be introduced to the liquid chromatography (LC) column, and mass spectrophotometer (MS). The plasma sample applied to MS may be ionized and quantified for analyzing the amount of ASA in plasma.
In one embodiment of the present invention, a mobile phase used in LC may be a mixture of acetonitrile and formic acid, preferably, a mixture of acetonitrile and 0.01% formic acid in a ratio ranging from 65 : 35 to 75 : 25 (v/v (%)), preferably, 70 : 30 (v/v (%)).
In MS, the plasma sample may be ionized in a negative ionization mode, and quantified in a multiple reaction monitoring (MRM) mode.
MS/MS spectrum results of ASA, SA and ibuprofen quantified in the
MRM mode are shown in Figs. 1 to 3, respectively.
As shown in Fig. 1, MS/MS spectrum of ASA quantified in MRM mode represents that Ql is about 179 (m/z), and Q3 is about 137 and 93 (m/z).
As shown in Fig. 2, MS/MS spectrum of SA quantified in MRM mode shows that Ql is about 137 (m/z), and Q3 is about 93 and 65 (m/z).
As shown in Fig. 3, MS/MS spectrum of ibuprofen quantified in MRM mode demonstrates that Ql is about 205 (m/z), and Q3 is about 161 (m/z).
The following Examples are intended to further illustrate the present invention without limiting its scope.
Example 1 : Construction of calibration curves
Standard samples of ASA and SA were prepared by sequentially diluting standard solutions of 100 μg/mL of ASA and 1 mg/mL of SA with a dog's blank plasma, respectively, giving final concentrations of 2 to 1 ,000 ng/mL for ASA and 20 to 10,000 ng/mL for SA. 20 μΐ, of the standard samples of different concentration levels were taken to each test tube with a cap. 50 iL of internal standard material (ibuprofen 500 ng/mL) was added to the test tube followed by adding 1 mL of methyl tert-butyl ether containing 0.5% acetic acid thereto. The mixture was centrifuged at 1 ,400 rpm for 10 min. A supernatant was collected, and then dried and concentrated at 35 °C using a vacuum dryer. The dried concentrates were dissolved in 500 μL of 50% acetonitrile (ACN) and subjected to the liquid chromatography-mass spectrometry (LC-MS) as follow.
The sample thus obtained was applied to LC with the following conditions.
<LC conditions>
System HP1100 series (Agillent Co., USA)
Column xterra MS C 18 (diameter 2.1 mm x length 50 mm, particle size 3.5 im, Waters)
Column temperature 30 °C
Mobile phase ACN/0.01 % formic acid= 70/30 (v/v (%)) Flow rate 200 nL/min
Injection volume 5 μL
Analysis time 5 min.
Then, the sample which passed through the LC column was applied to MS with the following conditions, and ionized in the negative ionization mode and then quantified in MRM mode as shown in Table 1.
<MS conditions>
System API 4000 Qtrap (Applied Biosystems/MDS
SCIEX, Canada)
Ionization mode Turbo ion spray ionization mode (negative) Curtain gas (CUR) 15 psi
Collision gas (CAD) Medium
Ion voltage -4500V
GS 1 50 psi
GS 2 40 psi
Turbo gas temperature 450 °C
CUR, CAD, GS (1, 2) Nitrogen.
<Table 1>
Calibration curves were constructed based on the ratio of peak areas for ASA and SA to those for the internal standard material, and calculated by a weighted (1/x) least squares regression. LC chromatograms for 250 ng/ml of ASA, and 78.125 ng/ml of SA are shown in Fig. 4.
Example 2: Sample analysis A blood sample was collected from a dog administered with aspirin, and stored at -70 °C . The sample was thawed at room temperature, well mixed in a desktop mixer for 0.5 min. 20 μΐ, of the resulting sample was transferred into a
test tube with a cap. 50 μΐ. of the internal standard material (ibuprofen 500 ng/mL) was added to the test tube followed by adding 1 mL of methyl tert-butyl ether containing 0.5% acetic acid thereto. The mixture was centrifuged at 1,400 rpm for 10 min. A supernatant was collected, and then dried and concentrated at 35 °C using a vacuum dryer. The dried concentrates were dissolved in 500 μL of 50% acetonitrile and subjected to the LC-MS according to the procedure described in Example 1. Quantification of ASA and SA in plasma was performed using the calibration curves constructed in Example 1.
As shown in the above, the method for analyzing aspirin in plasma with LC-MS according to the present invention can stably and easily analyze ASA and S A without loss of their amounts even after sampling.
While the invention has been described with respect to the above specific embodiments, it should be recognized that various modifications and changes may be made to the invention by those skilled in the art which also fall within the scope of the invention as defined by the appended claims.
Claims
1. A method for analyzing aspirin (ASA) in plasma with a liquid chromatography-mass spectrometry (LC-MS) which comprises the steps of:
1) adding an internal standard material and extracting solvent to a plasma sample, centrifuging the sample, and collecting a supernatant therefrom;
2) concentrating and dissolving the supernatant in acetonitrile; and
3) subjecting the resulting mixture obtained in step 2) to liquid chromatography-mass spectrometry for a quantitative analysis of aspirin in plasma.
2. The method of claim 1, wherein the internal standard material is ibuprofen.
3. The method of claim 1, wherein the extracting solvent is methyl tert- butyl ether (MTBE) containing 0.5% acetic acid.
4. The method of claim 1 , wherein the liquid chromatography is performed with a mobile phase which is a mixture of acetonitrile : 0.01% formic acid in a ratio ranging from 65 : 35 to 75 : 25 (v/v(%)).
5. The method of claim 4, wherein the liquid chromatography is performed with a mobile phase which is a mixture of acetonitrile : 0.01% formic acid in a ratio of 70 : 30 (v/v(%)).
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2010-0076890 | 2010-08-10 | ||
| KR1020100076890A KR20120014736A (en) | 2010-08-10 | 2010-08-10 | Analysis of Aspirin in Plasma Using Liquid Chromatography-Mass Spectrometry |
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| Publication Number | Publication Date |
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| WO2012020985A2 true WO2012020985A2 (en) | 2012-02-16 |
| WO2012020985A3 WO2012020985A3 (en) | 2012-05-31 |
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| PCT/KR2011/005843 Ceased WO2012020985A2 (en) | 2010-08-10 | 2011-08-10 | Method for analyzing aspirin in plasma with liquid chromatography-mass spectrometry |
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| KR (1) | KR20120014736A (en) |
| WO (1) | WO2012020985A2 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109085262A (en) * | 2018-08-03 | 2018-12-25 | 杭州佰勤医疗器械有限公司 | Serum plasma pharmaceutical extraction composition and application thereof |
| CN112345683A (en) * | 2020-11-24 | 2021-02-09 | 辽宁药联制药有限公司 | LC-MS simultaneous determination of ligustrazine and aspirin in blood plasma |
| CN112485340A (en) * | 2019-11-27 | 2021-03-12 | 南京品生医学检验实验室有限公司 | Method for detecting 1, 5-sorbitan in plasma by ultra-high performance liquid chromatography tandem mass spectrometry |
| CN114778737A (en) * | 2022-04-27 | 2022-07-22 | 天津国科医工科技发展有限公司 | Liquid chromatography detection sample pretreatment method capable of shortening time |
| CN114814018A (en) * | 2022-04-18 | 2022-07-29 | 合肥创新医药技术有限公司 | Method for determining doxylamine in human plasma through LC-MS/MS |
| CN117054542A (en) * | 2023-07-31 | 2023-11-14 | 四川省药品检验研究院(四川省医疗器械检测中心) | Method for detecting concentration of aspirin and salicylic acid in human plasma based on UPLC-MS/MS and application thereof |
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| KR101495450B1 (en) * | 2013-11-22 | 2015-03-02 | 한국마사회 | A method for analysis of acidic drugs in equine blood sample using on-column methylation |
| KR102033857B1 (en) | 2018-05-30 | 2019-10-17 | 경상대학교산학협력단 | Method for increasing the amino acid recovery of serum or plasma and Analytical method for determination of free amino acid in serum or plasma using LC-MS/MS |
-
2010
- 2010-08-10 KR KR1020100076890A patent/KR20120014736A/en not_active Ceased
-
2011
- 2011-08-10 WO PCT/KR2011/005843 patent/WO2012020985A2/en not_active Ceased
Non-Patent Citations (5)
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109085262A (en) * | 2018-08-03 | 2018-12-25 | 杭州佰勤医疗器械有限公司 | Serum plasma pharmaceutical extraction composition and application thereof |
| CN112485340A (en) * | 2019-11-27 | 2021-03-12 | 南京品生医学检验实验室有限公司 | Method for detecting 1, 5-sorbitan in plasma by ultra-high performance liquid chromatography tandem mass spectrometry |
| CN112345683A (en) * | 2020-11-24 | 2021-02-09 | 辽宁药联制药有限公司 | LC-MS simultaneous determination of ligustrazine and aspirin in blood plasma |
| CN114814018A (en) * | 2022-04-18 | 2022-07-29 | 合肥创新医药技术有限公司 | Method for determining doxylamine in human plasma through LC-MS/MS |
| CN114814018B (en) * | 2022-04-18 | 2024-05-24 | 合肥创新医药技术有限公司 | Method for determining doxylamine in human plasma by LC-MS/MS |
| CN114778737A (en) * | 2022-04-27 | 2022-07-22 | 天津国科医工科技发展有限公司 | Liquid chromatography detection sample pretreatment method capable of shortening time |
| CN114778737B (en) * | 2022-04-27 | 2024-05-10 | 天津国科医疗科技发展有限公司 | A method for sample pretreatment in liquid chromatography that can shorten the detection time |
| CN117054542A (en) * | 2023-07-31 | 2023-11-14 | 四川省药品检验研究院(四川省医疗器械检测中心) | Method for detecting concentration of aspirin and salicylic acid in human plasma based on UPLC-MS/MS and application thereof |
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| Publication number | Publication date |
|---|---|
| KR20120014736A (en) | 2012-02-20 |
| WO2012020985A3 (en) | 2012-05-31 |
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