JP5351709B2 - Drug analyzer - Google Patents

Description

  The present invention relates to a drug analyzer that analyzes a biological sample such as blood using a mass spectrometer, and more particularly, to a drug analyzer that includes a sample pretreatment device such as solid phase extraction.

  The mass spectrometry is an analysis method in which a measurement target component is ionized and measured based on the mass of generated ions. In particular, an analysis method called MS / MS, which performs mass spectrometry multiple times, can detect trace components in a sample solution containing a large amount of contaminant components with high sensitivity and high selectivity by fragmenting the measurement target component ions. It is used in many fields including biological samples. It is known that biological samples such as serum and urine are pretreated with a 96-well solid-phase extraction plate and measured with a mass spectrometer to quantify amino acids, carnitines, sugars, immunosuppressants and the like. (For example, refer to Patent Document 1).

  When mass spectrometry is applied to analysis of trace components in biological samples containing a lot of contaminants such as blood, a problem called ion suppression occurs in which the signal intensity of the target component is lower than when no contaminants are present. . In mass spectrometry, it is necessary to ionize the target component by an ionization method such as an electrospray ionization method. If a large amount of impurities are present at the same time when ionizing the target component, the ionization efficiency of the target component is lowered, and the quantitative result is affected. In the case of a blood sample, contaminants such as proteins and phospholipids that are contained in the sample in a large amount and have high ionization efficiency are known as components that lower the ionization efficiency of coexisting substances (see, for example, Non-Patent Document 1).

  Such a decrease in ionization efficiency, that is, ion suppression has an adverse effect on the accuracy or accuracy of the quantitative value, so some countermeasure is required. As an example of measures against ion suppression, there is a method of correcting a quantitative value using a stable isotope-labeled substance that can be regarded as causing the same ion suppression. However, synthesis of stable isotope-labeled substances is not only costly, but there is a problem that stable isotope-labeled substances cannot be produced for components that cannot be synthesized.

  Therefore, in Patent Document 1, a similar compound having a similar molecular structure is used as an internal standard substance in addition to a stable isotope labeling substance. In this way, when similar compounds are used as internal standard substances, the influence of contaminant components is not completely equivalent between the measurement target substance and the internal standard substance, and there is no guarantee that accurate values will be obtained even if correction is performed. It is.

  As another countermeasure against ion suppression, a method of reducing the influence of the contaminating component by separating the contaminating component and the component to be measured, for example, by performing a pretreatment of LC or solid phase extraction treatment is also used. Compared with a method using an expensive dedicated device such as LC, solid-phase extraction treatment can separate and concentrate a target component and remove impurities by a simple operation. In the case of a protein having a large molecular size, it is relatively easy to separate and remove the target component from the blood sample in the solid phase extraction process, but it is often not easy to separate and remove the phospholipid from the target target component. When a large amount of phospholipid is present in the solution, not only the measurement result is affected by mass spectrometry, but also the capture and recovery rate of the target component is reduced in the solid phase extraction process. Therefore, it is necessary to avoid contact between the phospholipid and the solid phase extraction agent.

  Here, as a method for selectively capturing phospholipids, there is a method using a specific interaction between a metal oxide such as titania or zirconia and a phosphorylated compound. For example, what concentrates a phospholipid selectively from an egg yolk origin lipid extract using a titania particle is known (for example, refer nonpatent literature 2). Further, in Patent Document 2, phospholipids and glycolipids are selectively separated from a cell-derived lipid extract using titania particles.

US Publication No. 2007/0404044 JP 2008-156571 A Yuan-Qing Xia and Mohammed Jemal, Rapid Commun, Mass Spectrom, 2009, 23, 2125-2138. Y. Ikeguchi and H. Nakamura, Anal. Sci., 2000, 16, 541-543.

  However, the methods described in Non-Patent Document 2 and Patent Document 2 perform a separate pretreatment before the treatment with titania particles. Both are targeted for extracts obtained by purifying only lipids by solvent extraction, and the selective adsorption of phospholipids to complex impurities such as blood samples is not considered.

  As a similar technique, a removal filter with a phospholipid supplementing function by zirconia is sold by Sigma-Aldrich. However, this is intended for serum and plasma samples, and in the case of blood samples, it is necessary to remove blood cells by centrifugation or the like to obtain plasma. This is because the filter is clogged and cannot be applied as it is. For this reason, this filter cannot be used when it is desired to measure a drug that is present in a large amount in blood cells, such as an immune inhibitor. In addition, when this filter is used, other contaminant components are removed and the target component is concentrated, so that a separate process such as solid phase extraction is required, resulting in a complicated pretreatment operation.

  An object of the present invention is to remove a contaminating component such as a protein or phospholipid contained in a blood sample, and at the same time, selectively capture a target target component, thereby providing a drug with a simple and highly efficient pretreatment device. An analyzer is provided.

(1) In order to achieve the above object, the present invention removes phospholipids, which are contaminant components, from a solution sample containing a drug in a pretreatment unit, and selects and purifies the drug to be measured by solid phase extraction. A drug analyzer for quantifying a drug in a mass spectrometric unit, comprising a pressure stirring mechanism that pressurizes and stirs a solution sample inside the solid phase extraction cartridge used for the solid phase extraction. It is.
With this configuration, contaminant components such as proteins and phospholipids contained in the blood sample are removed, and at the same time, the target target component is selectively captured, so that it becomes simple and highly efficient.

  (2) In the above (1), preferably, the pressure stirring mechanism is provided with an ultrasonic wave generator, and is stirred by the ultrasonic wave generator.

  (3) In the above (1), preferably, the solution sample inside the solid-phase extraction cartridge contains a metal oxide suspension.

  (4) In the above (3), preferably, the metal oxide is titanium oxide or zircon oxide.

  (5) In the above (3), preferably, the solid phase extraction cartridge is provided in a solid phase extraction agent, an upper filter provided on the solid phase extraction agent, and a lower portion of the solid phase extraction agent. And a lower filter, the component to be measured is extracted by the solid phase extraction agent of the solid phase extraction cartridge, and the upper filter removes the precipitate of the protein and the phosphate compound captured by the metal oxide. Is to do.

  According to the present invention, it is possible to perform simple and highly efficient pretreatment by removing contaminating components such as proteins and phospholipids contained in a blood sample and simultaneously selectively capturing a target component. .

It is a system block diagram which shows the structure of the drug analyzer by one Embodiment of this invention. It is explanatory drawing of the sample processing process in the drug analyzer by one Embodiment of this invention. It is sectional drawing which shows the structure of the pressurization stirring mechanism used for the drug analyzer by one Embodiment of this invention. It is sectional drawing which shows the structure of the pressurization stirring mechanism used for the drug analyzer by other embodiment of this invention.

  Embodiments of the present invention will be described in more detail with reference to the drawings. However, the present invention is not limited only to the following embodiments.

Hereinafter, the configuration and operation of a drug analyzer according to an embodiment of the present invention will be described with reference to FIGS.
First, the configuration of the drug analyzer according to the present embodiment will be described with reference to FIG.
FIG. 1 is a system block diagram showing the configuration of a drug analyzer according to an embodiment of the present invention.

  Here, analysis of an immunosuppressive agent will be described as an example of drug analysis in a blood sample using mass spectrometry. The immunosuppressive agent has blood cell transferability, and the immunosuppressive agent administered to the patient is present in the blood cells in the blood sample. Therefore, it is necessary to analyze a sample solution after performing a procedure called hemolysis that destroys blood cells using whole blood, not only a sample from which blood cells such as serum or plasma are removed.

  In the blood drug analyzer of this embodiment, a plurality of solid phase extraction cartridges 101 can be mounted on the endless track of the cartridge table 102. In the illustrated example, 18 solid-phase extraction cartridges 101 can be mounted. The cartridge table 102 rotates clockwise by a predetermined angle every predetermined time under the control of the control unit 120. For example, the cartridge table 102 rotates 20 degrees (= 360 degrees / 18) every 20 seconds.

  The cup table 103 is located below the cartridge table 102. The cup table 103 can mount a plurality of cups 104 on an endless track. At the position m of the cartridge table 102, the sample solution purified by the solid phase extraction cartridge 101 mounted on the cartridge table 102 is received by the cup 104 mounted on the cup table 103 positioned at the position x below. it can. The cup table 103 is added clockwise in accordance with the control of the control unit 120.

  The pressure load unit 105 is located above the cartridge table 102 and can pressurize the interior of the solid phase extraction cartridge 101. In the illustrated example, it is provided at five positions c, e, m, o, and p.

  A plurality of sample containers for storing blood samples can be attached to the sample disk 106. The sample probe 107 sucks the blood sample from the sample container attached to the sample disk 106 and discharges it to the solid phase extraction cartridge 101 at the position f of the cartridge table 102.

  A plurality of reagent containers storing a plurality of reagents are mounted on the reagent disk 108. The reagent probe 109 sucks a predetermined reagent from the reagent container mounted on the reagent disk 108 and discharges it to the solid phase extraction cartridge 101 at the position g and the position h.

  The methanol dispensers 110A and 110B can supply an organic solvent such as methanol to the solid-phase extraction cartridge 101 at the position l, the position b, and the position p of the cartridge table 102, respectively. The water dispensers 111A and 111B can supply an aqueous solvent such as distilled water to the solid phase extraction cartridge 101 at the position d and the position n of the cartridge table 102, respectively.

  The consumables rack 112 can transport the new solid phase extraction cartridge 101 to the position a of the cartridge table 102 and discard the used solid phase extraction cartridge 101 at the position n. In addition, the consumables rack 112 can transfer the new cup 104 to the cup table 103 at the position y, and discard the used cup 104 at the position y.

  The stirring mechanism 113 stirs a blood sample, a solvent, and the like supplied to the upper stage of the filter of the solid-phase extraction cartridge 101 at positions i, k, o, and q of the cartridge table 102.

  The suspension bottle 114 stores a titania particle suspension. The suspension stirring mechanism 115 stirs the titania particle suspension in the suspension bottle 114. The suspension probe 116 sucks the titania particle suspension from the suspension bottle 114 and discharges it to the solid-phase extraction cartridge 101 at the position j.

  The pressure stirring mechanism 117 can simultaneously stir and pressurize the sample solution in the solid phase extraction cartridge 102 at the position m. The feature of this embodiment resides in this pressure stirring mechanism 117, and details thereof will be described later with reference to FIG.

  The mass spectrometric unit 119 measures the immune inhibitor component in the solution. The pretreatment sample introduction unit 118 sucks the pretreated blood sample solution from the cup 104 at the position z of the cup table 103 and introduces it into the mass analysis unit 119.

  The control unit 120 analyzes the measurement result in the mass analysis unit 119, rotates the cartridge table 102, rotates the cup table 103, pressure loads the pressure load unit 105, rotates the sample disk 106, and the sample probe 107. Dispensing operation, rotating operation of reagent disk 108, dispensing operation of reagent probe 109, dispensing operation of methanol dispensers 110A, 110B, dispensing operation of water dispensers 111A, 111B, solid phase extraction cartridge 101 of consumables rack 112, etc. Transport / disposal operation of the cup 104, stirring operation of the stirring mechanism 113, stirring operation of the suspension stirring mechanism 115, dispensing operation of the suspension probe 116, pressure stirring operation of the pressure stirring mechanism 117, pretreatment sample introduction The dispensing operation of the unit 118 is controlled.

Next, the sample processing process in the drug analyzer according to the present embodiment will be described with reference to FIG.
FIG. 2 is an explanatory diagram of a sample processing step in the drug analyzer according to one embodiment of the present invention.

  Step 1 is a cartridge preparation operation, and the solid-phase extraction cartridge 101 is supplied from the consumables rack 112 and filled in the position a of the cartridge table 102. Thereafter, the cartridge table 102 rotates clockwise, and the filled solid-phase extraction cartridge 101 moves to the position b. After each step, the cartridge table 102 rotates 20 degrees in the clockwise direction to move the solid phase extraction cartridge 101 to the next position.

  Steps 2 and 3 are washing operations, and 200 μL of methanol is injected from the methanol dispenser 111 into the solid-phase extraction cartridge 101 at the position b. Next, it moves to the position c, pressure is applied to the inside of the cartridge from above by the pressure load part 105 at the position c, and the injected methanol is discharged from the lower part of the solid-phase extraction cartridge 101 to the outside. Of the pressure load section 105, four positions c, e, m, and o of the cartridge table 102 are provided with waste liquid treatment receptacles at the bottom, and the solution discharged by the pressure load is sent to the waste liquid receptacle. Collected. After methanol discharge, the cartridge moves to position d.

  Steps 4 and 5 are equilibration operations, and at position d, 200 μL of water is injected from the water dispenser 110 into the cartridge. Next, it moves to the position e, pressure is applied to the inside of the cartridge from above by the pressure load part 105 at the position e, and the injected water is discharged to the outside from the lower part of the solid phase extraction cartridge. After water discharge, the cartridge moves to position f.

  Step 6 is a sample injection operation. At position f, the blood sample solution stored in the sample disk 106 is dispensed by the sample probe 107 and injected into the solid-phase extraction cartridge 101 that has been equilibrated. After injecting the sample solution, the cartridge moves to position g.

  Step 7 is an internal standard injection operation. At a position g, 5 μL of an internal standard substance solution having a specified concentration stored in the reagent disk is dispensed by the reagent probe 109 and injected into the solid phase extraction cartridge 101 into which a blood sample has been injected. Is done. The internal standard substance is preferably an isotope-labeled form of the drug to be measured, but a compound having a similar molecular structure can be substituted. For example, in the case of the immunosuppressant tacrolimus, ascomycin, which is a similar compound, can be used as an internal standard substance as an internal standard. After the internal standard is added, the cartridge moves to position h.

  Steps 8 and 9 are hemolysis operations. At position h, 150 μL of 0.5 mol / L zinc sulfate aqueous solution stored on the reagent disk 108 is dispensed by the reagent probe 109 and injected into the solid-phase extraction cartridge 101. After injecting the aqueous zinc sulfate solution, the cartridge moves to position i. And it stirs with the stirring mechanism 113 installed in the position i, and destruction of the cell membrane of the erythrocyte which exists in the blood is accelerated | stimulated.

  The stirring mechanism 113 may be a mechanism that introduces and rotates a stirring rod with a spatula attached to the tip into the solution, or a mechanism that applies ultrasonic waves to the solution from the outside of the cartridge to stir the solution. . The stirring time can be arbitrarily set, but is normally used in about 10 seconds. In particular, by applying ultrasonic waves at a high temperature of 70 ° C. to 80 ° C., the efficiency of hemolysis is improved, and processing in a short time of about 10 seconds is possible. After stirring, the cartridge moves to position j.

  Steps 10 and 11 are phospholipid capture operations. At position j, the titania particle suspension stored in the suspension bottle 114 is dispensed by the suspension probe 116 and injected into the solid-phase extraction cartridge. . The suspension bottle is provided with a suspension stirring mechanism 115 and has a function of making the suspension state uniform during dispensing by stirring the suspension. Moreover, in order for titania to capture phospholipids, the solution needs to be in an acidic condition, and since the blood sample solution is usually near neutral, it is desirable that the titania particle suspension is acidic. For example, a suspension in which titania particles are suspended in a 10% aqueous formic acid solution at a rate of 0.5 mg / mL is applicable.

  After injecting the titania particle suspension, the cartridge moves to the position k, the titania particles and the blood sample solution are stirred by the stirring mechanism 113, and phosphorylated compounds such as phospholipids in the solution are captured on the surface of the titania particles. After stirring, the cartridge moves to position l.

  Step 12 is a protein precipitation generating operation. At position l, 200 μL of methanol is injected into the cartridge from the methanol dispenser 111, and aggregation of the protein present in the blood sample solution is started. After methanol injection, the cartridge moves to position m.

  Step 13 is a contaminant removal operation, in which a pressure is applied to the inside of the cartridge while stirring the blood sample solution by the pressure stirring mechanism 117 installed at the position m, and the sample solution is extracted to the solid phase extraction agent of the solid phase extraction cartridge 101. At the same time, the titania particles supplemented with phospholipids and the protein precipitate are removed from the solution by the filter above the solid phase extraction agent. Normally, titania particles or protein precipitates aggregate on the filter surface and cause clogging of the filter, but this mechanism stirs the solution simultaneously with pressurization, so it is possible to suppress clogging due to aggregation of the precipitate. is there.

  The immunosuppressant dissolved in the solution that has passed through the solid-phase extraction agent is captured by the solid-phase extraction agent by hydrophobic interaction with the solid-phase extraction agent, and other components pass through the cartridge together with the solution. It is sent to the waste liquid receiver installed at the bottom of the cartridge. After pressure loading, the cartridge moves to position n.

  Steps 14 and 15 are washing operations. At position n, 100 μL of water is injected from the water dispenser 110 into the solid-phase extraction cartridge 101 that has captured the immunosuppressant, and then the cartridge moves to position o. The pressure stirring mechanism 117 installed at the position o applies pressure while stirring water to allow the solid-phase extraction agent to pass through, and removes unnecessary components remaining on the surface of the solid-phase extraction agent. The passed water is sent to a waste liquid receiver installed at the bottom of the cartridge. After passing the liquid, the cartridge moves to the position p.

  Steps 16 and 17 are measurement component elution operations. After the methanol dispenser 111 injects 100 μL of methanol into the cartridge at the position p, the cartridge moves to the position q. The pressurized stirring mechanism 117 installed at the position q applies a pressure while stirring methanol to allow the solid-phase extractant to pass therethrough and elutes the immune inhibitor that is the measurement component trapped in the solid-phase extractant. The methanol solution containing the eluted immunosuppressant is collected by the cup 104 installed at the lower part of the position q. The cup 104 is located below the cartridge table 102 and can be fitted with a cup 104 that receives the sample solution eluted on the outer periphery of the table. The cup 104 can be mounted and discarded at the position y by the consumable rack 112. After elution of the components, the cartridge moves to the position r, the used cartridge is discarded in the consumables rack 112, and a new solid phase extraction cartridge 101 is filled at the position a.

  The eluate collected in the cup 104 is conveyed to the pretreatment sample introduction unit 118 by rotating the cup table. At the position z, the pretreatment sample introduction unit 118 sucks 20 μL of the eluate and introduces it into the mass analysis unit 119. Thereby, in the mass spectrometry part 119, the quantitative analysis of an immune inhibitor component is performed. The measurement signal is quantitatively processed by the control unit 120.

Next, the configuration and operation of the pressurized stirring mechanism 117 used in the drug analyzer according to the present embodiment will be described with reference to FIG.
FIG. 3 is a cross-sectional view showing a configuration of a pressure stirring mechanism used in the drug analyzer according to the embodiment of the present invention.

  The pressurizing and stirring mechanism 117 is a mechanism that can pressurize and simultaneously pressurize the solution inside the solid-phase extraction cartridge 101.

  The solid-phase extraction cartridge 101 has filters 101a and 101b in the upper and lower stages of the solid-phase extractant 101c and the solid-phase extractant 101c.

  As the solid-phase extraction agent 101c, a filler generally called a reverse phase system that has an action of adsorbing the immune inhibitor in the blood sample solution by hydrophobic interaction can be used. For example, fine particles in which an okdadecyl group is added to the surface of an organic polymer such as NOBIAS RP-OD1 manufactured by Hitachi High-Technologies Corporation can be used.

As the filter 101a in the upper stage of the phase extractant 101c, a filter having a filter diameter of about 0.45 to 2.0 μm can be used, but a filter having a diameter of about 1.0 μm is desirable.
On the upper part of the upper filter 101a of the solid-phase extraction cartridge 101, a suspension of titania particles supplemented with phospholipids in step 11 of FIG. 2 and protein precipitates generated in step 12 is held. The suspension is a mixture of a suspension and a dissolved body. Here, the diameter of the suspension is 0.45 μm or more. Therefore, the filter diameter of the upper filter 101a is set to 0.45 μm or more. On the other hand, if the filter diameter of the upper filter 101a is too large, the suspension is not captured by the upper filter 101a and passes therethrough. For example, the filter diameter of the upper filter 101a is 2.0 μm or less. Even in the range of the filter diameter of 0.45 to 2.0 μm, the filter tends to be clogged when close to 0.45 μm, and the permeated suspension tends to increase when close to 2.0 μm. About 0.0 μm is preferable.

  A pressure load unit 105 is closely fixed to the upper part of the solid phase extraction cartridge 101. The pressure load unit 105 includes a pressure load unit holder 105a and a pressurizing syringe 105b. The pressure load unit holder 105a is attached to the upper part of the solid phase extraction cartridge 101 without a gap. The pressure inside the cartridge 101 is increased by moving the pressurizing syringe 105b toward the solid-phase extraction cartridge 101 (the lower side in FIG. 3) to compress the gas inside the cartridge 101.

  Furthermore, in the present embodiment, an ultrasonic generator 113A that is an agitation mechanism capable of generating an ultrasonic wave and stirring the solution is installed near the upper filter 101a outside the solid-phase extraction cartridge 101. .

  Among the suspensions held on the upper part of the upper filter 101a of the solid-phase extraction cartridge 101, the suspension has a density distribution in which the upper part is small and the lower part is large. Therefore, when a pressure is applied by the pressure load unit 105 without using a stirring mechanism, a suspension having a high density in the lower part is easily clogged in the upper filter 101a.

  Therefore, in this embodiment, by stirring with the stirring mechanism 113A, the density distribution of the suspension inside the suspension is made uniform, and then the suspension is pressurized by the pressure load unit 105. The clogging of the filter 101a is suppressed.

  As described above, by simultaneously operating the stirring mechanism and the pressurizing mechanism, it is possible to simultaneously pressurize and stir the solution inside the solid phase extraction cartridge 101. By applying pressure, the solution passes through the upper filter 101a. Furthermore, the immunosuppressive agent dissolved in the solution is captured by the solid phase extraction agent 101c by hydrophobic interaction with the solid phase extraction agent 101c. Other components pass through the lower filter 101b of the cartridge together with the solution and are discharged from the lower portion of the cartridge.

  The filter diameter of the lower filter 101b is, for example, about 1.0 μm. The role of the lower filter 101b is to prevent the solid-phase extraction agent 101c in the upper part from leaking out of the cartridge. The average particle diameter of the solid phase extraction agent 101c is several tens of μm. Therefore, since the minimum particle diameter of the solid-phase extraction agent 101c is about several μm, the filter diameter is set to several μm or less in order to prevent the particles from flowing out.

  As described above, in this embodiment, it is possible to simultaneously remove proteins and phospholipids in a blood sample by a filter and concentrate a target component using a solid-phase extractant in one pressurizing process. . Since it can be performed in the same container as the hemolysis / protein removal process necessary for the pretreatment of the blood sample, no additional filter or pretreatment container is required, and the pretreatment process can be simplified.

Next, the configuration and operation of a drug analyzer according to another embodiment of the present invention will be described with reference to FIG. The configuration of the drug analyzer according to the present embodiment is the same as that shown in FIG. The sample processing process in the drug analyzer according to the present embodiment is the same as that shown in FIG.
FIG. 4 is a cross-sectional view showing a configuration of a pressure stirring mechanism used in a drug analyzer according to another embodiment of the present invention.

  The pressure stirring mechanism 117B can pressurize the solid-phase extraction cartridge 101 simultaneously with stirring. The pressurized stirring mechanism 117B includes a pressure load unit 105 and a stirring mechanism 113B.

  A pressure load unit 105 is closely fixed to the upper part of the solid phase extraction cartridge 101. The pressure load unit 105 includes a pressure load unit holder 105a and a pressurizing syringe 105b. The pressure load unit holder 105a is attached to the upper part of the solid phase extraction cartridge 101 without a gap. The pressure inside the cartridge 101 is increased by moving the pressurizing syringe 105b toward the solid-phase extraction cartridge 101 (leftward in FIG. 3) and compressing the gas inside the cartridge 101.

  The stirring mechanism 113B includes a stirring bar 113a equipped with a blade at the tip, and a motor 113b that rotates the stirring bar 105a. By rotating the stirring rod 113a by the motor 113b, the container inside the cartridge 101 can be stirred.

  Also in this embodiment, it is possible to simultaneously remove proteins and phospholipids in a blood sample by a filter and concentrate a target component using a solid-phase extraction agent in one pressurizing process. Since it can be performed in the same container as the hemolysis / protein removal process necessary for the pretreatment of the blood sample, no additional filter or pretreatment container is required, and the pretreatment process can be simplified.

In each of the above-described embodiments, the measurement result of tacrolimus in blood has been described. However, the present invention can be similarly applied to other immunosuppressive agents and other drugs. Moreover, it can be applied not only to blood but also to solution samples containing proteins and phospholipids such as biological extracts (such as urine and cerebrospinal fluid). In addition, a plurality of components contained in the sample solution can be simultaneously captured by the solid phase extraction agent and detected by mass spectrometry. In this case, it can be easily achieved by changing the detection conditions of the internal standard and the mass spectrometer according to the measurement target component.

DESCRIPTION OF SYMBOLS 101 ... Solid phase extraction cartridge 101a, 101b ... Filter 101c ... Solid phase extraction agent 102 ... Cartridge table 103 ... Cup table 104 ... Cup 105 ... Pressure load part 105a ... Pressure load part holder 105b ... Pressurizing syringe 106 ... Sample disk 107 ... Sample probe 108 ... Reagent disc 109 ... Reagent probe 110 ... Methanol dispenser 111 ... Water dispenser 112 ... Consumables rack 113 ... Agitating mechanism 114 ... Suspension bottle 115 ... Suspension agitating mechanism 116 ... Suspension probe 117 ... Pressure Stirring mechanism 118 ... pretreatment sample introduction unit 119 ... mass analysis unit 120 ... control unit 113A ... ultrasonic wave generation unit 113a ... stirring rod 113b ... motor

Claims (5)

A drug analyzer that removes phospholipids, which are contaminants, from a solution sample containing a drug in a pretreatment unit, selects and purifies the drug to be measured by solid-phase extraction, and quantifies the drug in a mass spectrometry unit There,
A drug analyzer comprising a pressure stirring mechanism that pressurizes and simultaneously stirs a solution sample in a solid phase extraction cartridge used for the solid phase extraction. The drug analyzer according to claim 1, wherein
The drug analyzing apparatus, wherein the pressure stirring mechanism includes an ultrasonic wave generation unit, and the ultrasonic wave generation unit performs stirring. The drug analyzer according to claim 1, wherein
The drug analysis apparatus characterized in that the solution sample inside the solid-phase extraction cartridge contains a metal oxide suspension. The drug analyzer according to claim 3, wherein
A drug analyzer, wherein the metal oxide is titanium oxide or zircon oxide. The drug analyzer according to claim 3, wherein
The solid phase extraction cartridge is composed of a solid phase extraction agent, an upper filter provided above the solid phase extraction agent, and a lower filter provided below the solid phase extraction agent,
A drug characterized in that a component to be measured is extracted with the solid-phase extraction agent of the solid-phase extraction cartridge, and protein precipitation is removed and a phosphate compound trapped in a metal oxide is removed with the upper filter. Analysis equipment.

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