JP2013011476A - Medicament-contaminated state inspecting tool, and medicament-contaminated state inspecting method using the inspecting tool - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a medicament-contaminated state inspecting tool and a medicament-contaminated state inspecting method using the inspecting tool, that allow a target component to be accurately and safely collected without causing individual differences between sampled amounts of the target component and without being influenced by properties of material of a monitoring place, and that are capable of accurately and quantitatively monitoring a contaminated state caused by a medicament in the monitoring place.SOLUTION: A medicament-contaminated state inspecting method includes the steps of: preparing a sheet-like member 10, and placing the sheet-like member 10 at an inspection target place 80 with a substrate 100 side upward; capturing a specimen on a surface of the substrate 100; adding water or an organic solvent to the captured specimen, and applying ultrasound to the solution or shaking the solution to dissolve and extract the specimen in the solution for obtaining an extraction liquid; and analyzing a specimen component in the extraction liquid by employing prescribed analysis means to obtain information on the specimen remaining on the substrate.

Description

  The present invention relates to a drug contamination state inspection tool and a drug contamination state inspection method using the inspection tool.

  An anticancer drug, which is a kind of drug, is a drug used for chemotherapy of malignant tumor (cancer). Anticancer agents exert their effects on cancer cells by causing fatal damage to genes in cancer cells or inhibiting cell division. On the other hand, many anticancer agents have been proven to be mutagenic, teratogenic, and carcinogenic and affect normal cells.

  Medical workers who handle anticancer drugs have a risk of inhaling the anticancer drug or adhering to the skin during preparation, administration, or disposal. In addition, the adhering anticancer drug may spread through the hands and soles, and may contaminate the entire ward as well as the medical staff. In particular, injections, which are the main dosage form of anticancer drugs, have been reported to be exposed to exposure risks such as inhalation of aerosol particles, needle sticks, vials, and contact with contaminated surfaces of ampoules when handling ampoules and vials. ing.

  In order to protect medical staff who handle anticancer drugs from exposure and environmental pollution, the Japan Hospital Pharmacists Association formulated guidelines on the handling of anticancer drugs in 1991 (revised in 2005, 2007 and 2009). . These guidelines include the use of protective clothing, masks and gloves, improvement of drug preparation and administration procedures, introduction of safety cabinets, etc. when medical workers handle anticancer drugs in their daily work. It is stated that it should be noted in daily work in order not to contaminate the medical environment, as well as not to be exposed. On the other hand, Chapter 797 of the US Pharmacopoeia General Rules recommends regular monitoring of the state of contamination by anticancer drugs, but there is no such recommendation yet in Japan, and it is recommended for each medical institution. The current situation is that the environment for handling cancer drugs is different.

  In order to prevent medical workers' exposure and contamination of the medical environment, while complying with the protection measures and guidelines of medical workers, we regularly monitor the state of contamination with anticancer drugs, and in daily work It is important to continually review the handling of anticancer drugs.

  Therefore, conventionally, as a method for monitoring the residual amount of an anticancer drug remaining within a certain area, a test method called a wiping method (hereinafter referred to as “swab method”) has been implemented in medical institutions. (For example, refer nonpatent literature 1.).

EX Control Japan Co., Ltd., “Wipe Inspection Method (Excerpt)”, [online], Internet <URL: http://www.exposurecontrol.jp/pdf/inspectingcommissions.pdf>

  The swab method described in Non-Patent Document 1 will be described. First, for example, a medicine such as sodium hydroxide is sprayed on a test surface having a constant area of 70 cm × 70 cm. Next, the test surface is strongly wiped with a wiping member such as cotton or gauze, and the anticancer agent adhering to the test surface is physically collected together with the drug. Thereafter, pretreatment is performed to extract the anticancer agent of the target component from the wiping member, and measurement is performed by a predetermined analysis means such as mass spectrometry.

  As a general problem of the swab method described in Non-Patent Document 1, it is common that the wiping operation is performed by an on-site worker engaged in medical treatment, and when wiping the test surface, a wiping member Therefore, it is said that the strength of pressing the test surface may vary depending on the inspector, so that there is an individual difference in the amount of the target component collected. Further, when wiping the test surface with a wiping member, a chemical such as sodium hydroxide that should be handled with care is used, which is not preferable for safety.

  On the other hand, in order to monitor the state of contamination by an anticancer agent, it is necessary to carry out it at a place related to the preparation and administration of the anticancer agent. Specifically, the tray to be loaded into the drug adjustment room, the floor at the entrance of the drug adjustment room, the floor surface in front of the safety cabinet, the safety cabinet, the desk, the work table on which the infusion line is set, the floor surface in front of the work table, the disease It is the floor under the drip stand in the room, a nurse station, etc. There are various materials such as metal surfaces, concrete surfaces, tile surfaces, etc. for the test surfaces in these places.

  However, the conventional swab method, in addition to the above-mentioned problems, accurately collects the target component if the target component is wiped from the test surface of a different material with a wiping member even if the sampling location is the same. However, there is a problem that the reliability of measurement is poor.

  In addition, the swab method can only grasp the total accumulated amount of anticancer drugs from the past at the monitoring location, and the anti-accumulation accumulated within a period intended by the examiner, such as one week or one month from a certain point in time. I can't figure out how much cancer drugs are available.

  Although it can be considered that the test surface at the monitoring location is cleaned by some method and the anticancer agent present on the test surface is wiped off after a certain period of time, as described above, the swab method is Since it has a fundamental problem that it is difficult to accurately collect the target component, it is not easy to monitor the amount of the anticancer drug present on the test surface after a certain period of time has elapsed from a certain point in time. Thus, the conventional swab method is not an appropriate method for quantitatively monitoring the state of contamination by anticancer agents.

  Therefore, as a result of intensive studies to solve the problems of the above-mentioned swab method, the present inventors have installed a clean sheet-like member at a monitoring place and collected an anticancer agent attached to the surface. It has been found that there is no individual difference in the amount of the target component collected by the inspector, and that the target component can be accurately and safely collected regardless of the environment and conditions of the monitoring place. Then, by analyzing the collected anticancer agent using a predetermined analysis means to obtain information on the anticancer agent, the state of contamination by the anticancer agent at the monitoring location can be accurately and quantitatively determined. The inventors have found that monitoring is possible and have arrived at the present invention.

  Accordingly, the present invention has been made with the object of solving such problems, and the object of the present invention is that there is no individual difference in the amount of the target component collected, and the material of the monitoring place is A drug contamination state inspection tool capable of accurately and safely collecting the target component without being influenced and accurately and quantitatively monitoring the state of contamination by the drug at the monitoring site, and of the drug using the inspection tool It is to provide a contamination state inspection method. Another object of the present invention is to provide a drug contamination state inspection tool that can easily monitor the amount of drug accumulated after a certain period of time from a certain point in time, and a drug contamination state inspection method using the inspection tool. That is.

  The drug contamination state test tool of the present invention includes at least a sheet-like member, and a sample collection container including a sealing portion that seals the opening after the accommodated item is accommodated in the opening from the opening. These are housed in a tub that closes the interior to make the inside substantially sealed.

  The method for inspecting a contamination state of a medicine using the contamination state inspection tool of the present invention includes a step of preparing a sheet-like member, installing the sheet-like member at a place to be inspected, and capturing a specimen on the surface of the sheet-like member A step of capturing the specimen on the surface of the substrate, adding water or an organic solvent to the captured specimen, applying an ultrasonic wave to the solution, or shaking the solution, thereby bringing the specimen into the solution. It includes a step of obtaining an extract by dissolving and extracting, and a step of analyzing specimen components in the extract using predetermined analysis means to obtain information on the specimen remaining on the substrate.

  According to the present invention, there is no individual difference in the collection amount of the target component, and the target component can be collected accurately and safely without being affected by the environment and conditions of the monitoring location. It is possible to provide a drug contamination state inspection tool capable of accurately and quantitatively monitoring the state, and a drug contamination state inspection method using the inspection tool. In addition, the present invention has an effect that it is possible to easily monitor the amount of medicine accumulated after a certain period of time from a certain point in time.

It is the perspective view which showed the whole test | inspection kit which concerns on this Embodiment. It is a top view explaining a transparent resin sheet. It is a perspective view explaining the state which peels a peeling film from a transparent resin sheet. It is a perspective view which shows the state which installed (attached) the transparent resin sheet in the predetermined place. It is a perspective view explaining the state accommodated in the transparent resin sheet storage container which extract | collected the test substance. It is a perspective view explaining the state sealed and accommodated in the transparent resin sheet storage container which extract | collected the test substance. It is the top view which showed the recording paper. It is the perspective view which showed the state which delivers a test substance (accommodated in a storage container) to a test | inspection department. It is the top view which showed the experimental result of the monitoring experiment using a test | inspection kit.

  Hereinafter, a drug contamination state inspection tool (hereinafter simply referred to as “test kit”) and a drug contamination state inspection method using the test kit according to embodiments of the present invention will be described with reference to the accompanying drawings. In the following description, terms and directions (for example, “front surface”, “back surface”, “upper part”, “lower part”, etc.) are used for convenience, but these are for facilitating understanding of the invention. The technical scope of the present invention is not limited by the meaning of these terms. Further, the following description is merely illustrative in nature, and is not intended to limit the present invention, its application, or its use.

  In addition, the concept of the “medicine” of the present invention includes chemical substances that can inhibit the health of the human body due to incorrect administration, exposure or environmental pollution, and can cause serious effects including death. Specifically, the International Agency for Research on Cancer (IARC) is Group 1 (carcinogenic to humans is recognized), Group 2A (possibly carcinogenic to humans), Group 2B (carcinogenic to humans). In addition to chemical substances classified as), legal drugs such as narcotics, stimulants, psychotropic drugs, insecticides such as dichlorodiphenyltrichloroethane (DDT), fungicides, rodenticides, herbicides Pesticides such as repellents and attractants.

  Among the above-mentioned drugs, chemical substances belonging to Group 1 include cyclophosphamide, melphalan, tamoxifen, etoposide / cisplatin / bleomycin concomitant, formaldehyde and the like. Chemical substances belonging to Group 2A include cisplatin, etoposide, lomustine, adriamycin and the like. Chemical substances belonging to Group 2B include bleomycin, daunomycin, methylthiouracil, mitomycin C, propylthiouracil, naphthalene and the like. In addition, ifosfamide, an anticancer agent not belonging to the above Groups 1, 2A and 2B, is also included. In the following embodiments, among the drugs, cyclophosphamide and ifosfamide anticancer agents will be exemplified and described.

[Inspection kit]
As shown in FIG. 1, a test kit 1 according to the present embodiment includes a transparent resin sheet (sheet-like member) 10, a storage container (specimen collection container) 11, gloves 12, recording paper 13, and a courier invoice. 14 and a sample collection method manual (not shown). For example, 10 sets of each of the transparent resin sheet 10, the container 11, and the gloves 12 are prepared. And these are accommodated in the bag 15 for conveyance.

  The transparent resin sheet 10 is installed in a predetermined place in order to monitor the contamination state of the anticancer agent in a place related to the preparation and administration of the anticancer agent, and an aerosol or liquid is prepared through the preparation or administration. Anti-cancer drug (hereinafter simply referred to as “specimen”) that has spread into the air in the form of droplets or powder, or a transparent transparent resin that has been dispersed by the scattered specimen through the hands, shoe soles, etc. It is captured on the surface of the sheet 10.

  The transparent resin sheet 10 is formed of, for example, a 10 cm × 10 cm square resin film of polyethylene terephthalate having a thickness of 0.3 mm. As shown in FIG. 2, the transparent resin sheet 10 is a two-layered sheet-like member in which an adhesive layer 101 is laminated on a base material 100. A release film 102 is coated on the surface of the adhesive layer 101 opposite to the substrate 100 side.

  As shown in FIG. 2A, a sample ID 103 indicating a specimen is printed on the surface (non-adhesive) of the base material 100 at the upper right corner position of the base material 100. As shown in FIG. 2B, the release film 102 has a notch 104 in which a part of the upper left corner is cut. This is because the inspector wearing the gloves 12 can smoothly perform the work of peeling the release film 102 from the substrate 100.

  Further, as shown in the figure, a round seal 105 is attached at a position corresponding to the sample ID 103 and at an upper left corner position of the release film 102. This is to prevent the substrate 100 from being accidentally discarded when the transparent resin sheet 10 is used by clearly distinguishing the substrate 100 and the release film 102.

  The transparent resin sheet 10 of the present embodiment has the adhesive layer 101 on one side of the substrate 100, but in the sheet-like member of the present invention, the sheet-like member only of the substrate 100 without the adhesive layer. In addition, for example, the first base material has adhesive layers on both surfaces (front surface and back surface), one adhesive layer is covered with a release film, and the other adhesive layer has a second substrate. It may be a sheet-like member having a multilayer structure in which the material is covered. The procedure for collecting the specimen using the multilayered sheet-like member will be described later. Moreover, the shape of the transparent resin sheet 10 is not limited to a square, and may be a rectangular shape having short and long sides, a polygonal shape including a triangle, a quadrilateral, or a circular shape. . The size can also be changed as appropriate according to the installation location.

  Moreover, in this Embodiment, although the transparent resin sheet 10 formed with the polyethylene terephthalate is illustrated as a sheet-like member, it is not limited to this. As an alternative to polyethylene terephthalate, it has been confirmed by experiments by the inventors that polytetrafluoroethylene (PTFE), a stainless steel thin plate with a smooth surface, and the like can suitably capture the specimen. However, a stainless steel plate is not suitable for installation on a curved floor and is heavy. In addition, polytetrafluoroethylene is strong and is not suitable for installation on a curved floor. Considering these matters, a transparent resin sheet made of polyethylene terephthalate having a light weight and appropriate flexibility is suitable as the sheet-like member of the present invention. In addition, the sheet-like member of the present invention does not necessarily need to be transparent, and may be colored so that it can be visually recognized when installed in a predetermined place.

  Returning to FIG. 1, the container 11 is a substantially box-shaped container for hermetically housing the transparent resin sheet 10 that has captured the specimen. As shown in the drawing, the storage container 11 includes a container main body 110 having an opening for taking in and out the stored object (in this case, the transparent resin sheet 10), and a lid body that is detachably fitted so as to close the opening. 111. The container body 110 is made of, for example, polypropylene, and the lid body 111 is made of, for example, styrene resin.

  Referring to FIGS. 5 and 6, the container 11 has a flat bottom 115 of the container body 110. The transparent resin sheet 10 is placed on the flat bottom portion 115. Further, a locking piece 117 is formed on the peripheral edge of the lid 111, and a groove (sealing part) (not shown) for locking the locking piece 117 is formed on the peripheral edge of the container body 110. Accordingly, when the lid body 111 is fitted to the container body 110, the locking piece 117 is engaged with the groove, and the lid body 111 can be locked so as not to be detached from the container body 110. In addition, when removing the lid 111 from the container main body 110, the groove | channel is destroyed by picking the lock release mechanism 118 by hand and pulling outward, and the lid 111 can be removed.

  As long as the transparent resin sheet 10 can be horizontally placed on the bottom portion 115 and the lid 111 is not easily detached from the container main body 110 when the lid is tightened, the storage container 11 may have any shape. The goal can be fully achieved. The material is not limited to resin but may be, for example, an aluminum or stainless steel container. Further, for example, a transparent sheet material made of polypropylene is used on the outer surface to form a water-sealed bag shape so that water does not enter, and after inserting the transparent resin sheet 10 into the inside through the opening, It may be a container (specimen collection container) provided with a plastic fastener (sealing part) such as Ziploc (registered trademark: Ziplock) that hermetically closes the opening.

  The gloves 12 prevent the specimen from adhering to the examiner's finger and prevent deposits, sweat, oil, etc. on the examiner's finger from adhering to the transparent resin sheet 10. For this reason, it is preferable that the gloves 12 are commercially available for medical workers.

  As shown in FIGS. 1 and 7, the recording sheet 13 is a recording medium for recording necessary items regarding sample collection. Specifically, the sample ID number, the place where the transparent resin sheet 10 was installed (sampling place), the name of the target drug as a contamination source, the date when the transparent resin sheet 10 was installed, and the date when the transparent resin sheet 10 was collected This is a so-called check sheet in which each item is tabulated.

  Returning to FIG. 1, for example, the bag 15 is formed by bonding or sewing a material obtained by laminating a foamed polyethylene sheet and a plastic film having an aluminum vapor deposition layer on one side into a bag shape. It is a well-known cold insulation bag provided with a pair of gussets 151 and 152 at the side edges. As illustrated, a plurality of protrusions 153 are formed on the gusset portion 151. A plurality of holes 154 are formed in the gusset portion 152 at positions where the protrusions 153 face each other. While the gusset portions 151 and 152 are brought into contact with each other and the protrusion 153 is inserted into the hole 154, the flange 15 is substantially sealed.

  The form of the ridge 15 may be any form of ridge as long as the contents are not visually recognized from the outside and the inside can be substantially sealed by closing the opening. A description of the home delivery invoice 14 is omitted.

  Next, a method for inspecting a contamination state of a drug using the inspection kit of the present embodiment will be described.

[Sample collection]
First, the inspector takes out the gloves 12 from the heel 15 and wears the gloves 12 in both hands. Next, as shown in FIG. 3, the upper right corner position of the transparent resin sheet 10 (base material 100) on which the sample ID 103 is printed is grasped with a finger, and the notch 104 of the release film 102 is grasped with the other finger. The release film 102 is peeled off from the substrate 100, and the peeled release film 102 is discarded.

  Subsequently, the transparent resin sheet 10 is installed at a predetermined place 80 related to preparation and administration of the anticancer agent. Specifically, as shown in FIG. 4, the base material 100 is directly attached to a predetermined place 80 with the sample ID 103 printed side of the base material 100 facing upward (the adhesive layer 101 side facing downward). . In addition, when installing the sheet-like member having the multilayer structure described above at a predetermined location 80, the release film is peeled off from the first base material, and the second base material is faced directly on the installation surface. A specimen is captured on the surface of the second substrate.

  As described in [Summary of the Invention], the predetermined place 80 is set with a tray for carrying into the medicine adjustment room, a floor at the entrance of the medicine adjustment room, a floor surface in front of the safety cabinet, a safety cabinet, a desk, and an infusion line. A work table, a floor surface in front of the work table, a floor surface under an infusion table in a hospital room, a nurse station, and the like. The surface to which the substrate 100 is attached is different in material such as a metal surface, a concrete surface, a tile surface, and the surface shape is various such as a curved surface or an uneven surface, but the transparent resin sheet 10 of the present embodiment is It can be easily attached to any place without being restricted by the material of the attaching place.

  When the attachment of the substrate 100 to the predetermined place 80 is completed, the substrate 100 is left as it is for a certain period. This period is a fixed period such as one week or one month that is intentionally set by the inspector. That is, the amount of the sample captured on the surface of the base material 100 is measured during the period from the date when the base material 100 is attached to the time when the base material 100 is collected. In addition, the gloves 12 worn when the base material 100 is attached are discarded.

  The inspector uses the number of the sample ID 103 printed at the upper right corner position of the base material 100, the place where the base material 100 is pasted (sampling place), the drug name “cyclophosphamide”, “ The selection of “Ifosfamide” and the date on which the substrate 100 is pasted at a predetermined location 80 are recorded on the recording paper 13 (see FIG. 7).

  After the predetermined period of time, the inspector wears the gloves 12 in both hands, and then peels off the base material 100 attached to a predetermined place 80, with the side on which the sample ID 103 of the base material 100 is printed facing upward. The base material 100 is directly attached to the bottom 115 of the container main body 110 (with the adhesive layer 101 facing downward) (see FIG. 5). Subsequently, the base body 100 is hermetically accommodated in the container 11 by fitting the lid 111 to the container body 110 (see FIG. 6). And the date which peeled off the base material 100 from the predetermined place 80 and was collect | recovered is recorded on the recording paper 13 (refer FIG. 7). The gloves 12 worn when collecting the base material 100 are discarded.

  When collecting the sheet-like member having the multilayer structure described above, the first base material is peeled off from the predetermined place 80, the second base material is peeled off from the first base material, and the second base material is removed. The base material may be hermetically housed in a housing container provided with the above-described Ziploc (registered trademark: Ziplock) type plastic fastener (sealing portion).

  When the above-described operation is completed, as shown in FIG. 8, after the storage container 11 and the recording paper 13 in which the base material 100 is hermetically stored are stored in the bag 15, the gusset portions 151 and 152 of the bag 15 are brought into contact with each other. 15 is substantially sealed, and a courier invoice 14 is attached to the side surface of the bag 15 and delivered to the inspection department. In the present embodiment, an example has been described in which the inspector attaches the courier invoice 14 to the bag 15 and delivers the bag 15 (specimen) to the inspection department by the courier. However, the present invention is not limited to this. The inspector may bring the bag 15 (specimen) directly into the inspection department.

  As described above, the test kit 1 according to the present embodiment does not wipe off and collect the sample as in the prior art, but only captures the sample on the surface of the clean substrate 100. In addition to being able to collect, it is possible to accurately grasp the contamination state due to the specimen. Further, there is no variation in the amount of the target component collected by the inspector. Since the amount of the target component to be collected is accurate, it is possible to accurately grasp the contamination state of the sample that has spread over a certain period of time that is intentionally set by the examiner.

[Sample Extraction Method and Analyzing Method of Residual Amount of Extracted Sample]
From here, a method for extracting a sample attached to the surface of the substrate 100 and a method for analyzing how much the amount of the sample has been extracted will be described. In the following analysis examples, cyclophosphamide is exemplified and described as a sample.

  Regarding the sample extraction method and the analysis method of the extracted sample amount described below, specificity, linearity, detection limit, and recovery rate (accuracy) were evaluated in advance experiments by the inventors. All the evaluation items are confirmed to meet the evaluation criteria.

  Here, the specificity is a method of measuring only it specifically without being influenced by other. Linearity is the ability to indicate that the concentration (content) of the analyte (specimen) and the measurement result are in a proportional relationship within a certain concentration range. The detection limit is literally the lowest amount that can be detected for the analyte (specimen). The recovery rate (accuracy) is the degree of agreement between an average value obtained from a sufficiently large number of test results and an approved standard value. As described above, the sample extraction method and the analysis method of the extracted sample amount to be described below are performed by validated methods.

1. With respect to the container 11 in which the sample solution preparation substrate 100 is hermetically housed, the lock release mechanism 118 is picked by hand and pulled outward to remove the lid 111 from the container body 110 (that is, the state shown in FIG. 5). .) Subsequently, 10 mL of pure water is added to the container body 110, and then the ultrasonic transmitter is operated to apply ultrasonic vibration to the aqueous solution for 5 minutes. Thereby, the specimen (cyclophosphamide) attached to the base material 100 is dissolved in pure water, and a uniform sample solution is obtained. In addition, it can replace with an ultrasonic transmitter and can also obtain uniform aqueous solution by shaking the container main body 110, for example with a desktop shaker. When insoluble substances such as dust are contained in the aqueous solution, the aqueous solution may be filtered with, for example, a filter made of polytetrafluoroethylene (PTFE) that does not adsorb the specimen. In this preparation method, for example, a specimen captured only on the surface of the sheet-like member of the base material 100 having no adhesive layer or a specimen captured on the surface of the second base material of the sheet-like member having a multilayer structure is extracted. Is particularly preferred.

  As described above, the specimen extraction according to the present embodiment is performed by adding pure water to the substrate 100 to which the specimen is attached to form an aqueous solution, and applying ultrasonic waves to the aqueous solution or shaking the aqueous solution. Thus, an aqueous solution in which the specimen is uniformly dissolved is obtained mechanically. For this reason, skill is not required for extraction of the aqueous solution in which the specimen is uniformly dissolved, and anyone can easily extract the aqueous solution.

  Instead of the specimen extraction method described above, the following method is also possible. First, prepare a 3cm x 3cm JP absorbent cotton (first absorbent cotton) moistened with 1mL of 70% ethanol (disinfecting ethanol) and a 3cm x 3cm JP absorbent cotton (second absorbent cotton) that does not wet the solution. After wiping off the surface of the substrate 100 to which the specimen is attached with the former absorbent cotton, the surface of the substrate 100 is again wiped with the latter absorbent cotton. Next, the two absorbent cottons after wiping are put into a centrifugal sedimentation tube (container), 9 mL of pure water is added to the centrifugal sedimentation tube, this is attached to a mixer and shaken vigorously for 10 minutes to obtain a sample solution.

2. Preparation of Blank Solution An unused base material 100 is attached to the bottom 115 of an unused container body 110, 10 mL of pure water is added to the container body 110, and then an ultrasonic transmitter is operated to make the aqueous solution super A blank solution is obtained by applying sonic vibration for 5 minutes. In addition, it can replace with an ultrasonic transmitter and a blank solution can also be obtained by shaking the container main body 110, for example with a desktop shaker.

  As for the preparation of the blank solution, similarly to the preparation of the sample solution described above, 3 cm × 3 cm of JP absorbent cotton moistened with 1 mL of 70% ethanol (disinfecting ethanol) and 3 cm × 3 cm of JP absorbent cotton not moistened with the solution. After preparing and wiping the surface of the unused substrate 100 with the former absorbent cotton, the surface of the substrate 100 is again wiped with the latter absorbent cotton. Next, the two absorbent cottons after wiping may be put into a centrifugal sedimentation tube, 9 mL of pure water may be added to the centrifugal sedimentation tube, and this may be attached to a mixer and vigorously shaken for 10 minutes to obtain a blank solution.

3. Preparation of standard solution About 22 mg of cyclophosphamide standard product is weighed accurately, dissolved in methanol to make exactly 200 mL, and used as a standard solution of cyclophosphamide. Weigh accurately 2 mL of cyclophosphamide standard stock solution and add water to make exactly 200 mL. Weigh accurately 2.5 mL of this solution and add water to make exactly 100 mL. Pipet 2 mL of this solution, add water to make exactly 100 mL, and use this solution as the standard solution (cyclophosphamide: 0.5 ng / mL).

4). Method for Analyzing Residual Amount of Specimen Using 5 μL of the above sample solution and standard solution, these were tested by high performance liquid chromatography / mass spectrometry under the following apparatus conditions, and the peak area _{AT of} cyclophosphamide in each solution And _AS is measured. High-performance liquid chromatograph mass spectrometry uses a high-performance liquid chromatograph (HPLC) that excels in sample separation and analysis, and a device that connects a mass spectrometer (MS) that excels in sensitive analysis and structural analysis. This is an analysis method in which components separated in a graph are ionized and guided to a mass spectrometer, where they are divided by mass level to detect a target component. In this embodiment, a UPLC (Ultra Performance LC) is used in the LC section, and a liquid chromatograph / tandem mass spectrometer (LC / MS / MS) equipped with a tandem quadrupole mass spectrometer is used in the MS section. . The resulting peak areas A _T and A _S are substituted into Equation 1 to calculate the residual amount of the specimen (cyclophosphamide).

[UPLC condition]
Apparatus: ACQUITY UPLC (manufactured by Waters)
Column: ACQUITY UPLC HSS T3, 1.8μm, ID 2.1mm, length 50mm
Column temperature: 40 ° C
Injection volume: 5μL
Sample cooler: 10 ℃
Table 1 shows the gradient conditions.

[Table 1]

[MS / MS conditions]
Detector: ZEVO TQ MS (manufactured by Waters)
Ionization mode: ESI +
Measurement conditions: Target product ion of 105.86 (m / Z) generated by the decomposition of 216.13 (m / Z) precursor ion in MRM mode cyclophosphamide.

[Equation 1]
Residual amount of sample (ng) = Ws1 × P / 100 × 261.09 / 279.1 × A _T / A _S × 1 / 4,000,000 × 1,000,000
Where Ws1: Standard amount of cyclophosphamide standard (mg)
P: Content
261.09 / 279.1: Cyclophosphamide anhydride displayed amount / cyclophosphamide monohydrate displayed amount
1 / 4,000,000: dilution factor, 1,000,000: unit conversion factor (mg → ng)

In this analysis example, cyclophosphamide is exemplified and described as a sample. However, when the sample is, for example, ifosfamide, the following is performed. First, a standard solution of ifosfamide at 0.25 ng / m is prepared. When analyzing a sample, the components of ifosfamide separated by liquid chromatography are ionized and guided to a mass spectrometer, and 91.87 (m / Z) product ions generated by decomposition of 216.13 (m / Z) precursor ions in ifosfamide. the measuring the peak area a _T and a _S of ifosfamide as a target. Then, the residual amount of the sample (ifosfamide) is calculated by substituting the obtained peak areas _AT and _AS into [Equation 2].

[Equation 2]
Residual amounts of analyte (ng) = Ws2 × P / 100 × A T / A S × 1 / 8,000,000 × 1,000,000
Where Ws2: Standard amount of ifosfamide standard (mg)
1 / 8,000,000: dilution factor

  In the present embodiment, the sample extracted from the surface of the base material 100 is implemented by an analysis method using a liquid chromatograph / tandem mass spectrometer (LC / MS / MS), but the present invention is not limited to this. . For example, high performance liquid chromatography, liquid chromatograph mass spectrometer, gas chromatography, gas chromatograph-mass spectrometer, gas chromatography tandem mass spectrometer, inductively coupled plasma emission spectrometer, inductively coupled plasma mass spectrometer, UV meter, fluorescence It is also possible to carry out with each analysis method using a photometer or the like.

[Monitoring experiment using test kit]
With the cooperation of a medical institution that has established an anticancer drug adjustment room, the diffusion status of the anticancer drug in the medical institution for a predetermined period (one week) was monitored. The result is shown in FIG. In the figure, “BSC” is a safety cabinet used when preparing an anticancer agent. As shown in the figure, cyclophosphamide was detected from all sampling points including the floor in front of the safety cabinet.

  As explained in [Background Art], Chapter 797 of the US Pharmacopoeia recommends regular monitoring of anticancer drug contamination. In the future, it is expected that monitoring of pollution will be carried out regularly in Japan in conformity with it.

  The drug contamination state inspection tool of the present invention and the drug contamination state inspection method using the inspection tool include, in addition to the above-described contamination state monitoring by the drug, for example, contamination state due to harmful elements such as cadmium, lead and mercury. It can also be applied to monitoring.

1 Inspection kit 10 Transparent resin sheet (sheet-like member)
11 Container 12 Gloves 13 Recording Paper 14 Courier Invoice 15 鞄 100 Base Material 101 Adhesive Layer 102 Release Film 103 Sample ID
104 Notch 110 Container body 111 Lid 115 Bottom of container body

Claims (10)

A sheet-like member;
Including at least a specimen collection container provided with a sealing portion for sealing the opening after accommodating the contents from the opening inside,
A drug contamination state inspecting tool which is housed in a bag whose inside is substantially sealed by closing the opening.   The drug contamination state inspection tool according to claim 1, wherein the sheet-like member has an adhesive layer formed on at least one surface of a base material.   The drug contamination state inspection tool according to claim 2, wherein the base material is formed of a resin film.   4. The sample collection container according to claim 1, wherein the sample collection container includes a container main body in which an opening for taking in and out the contained material is formed, and a lid body that is detachably fitted so as to close the opening. The contamination check device for the medicine described. Preparing a sheet-like member, and installing the sheet-like member in a place to be inspected;
Capturing a specimen on the surface of the sheet-like member;
Adding water or an organic solvent to the specimen, applying ultrasonic waves to the solution, or shaking the solution to dissolve and extract the specimen in the solution to obtain an extract;
A method for inspecting a contamination state of a drug, comprising: analyzing a sample component in the extract using a predetermined analysis unit to obtain information on a sample remaining on the substrate. Instead of adding water or an organic solvent to the specimen and applying ultrasonic waves to the solution or shaking the solution, the specimen is dissolved and extracted in the solution to obtain an extract,
A first absorbent cotton moistened with a disinfectant and a second absorbent cotton not moistened with the disinfectant are prepared. After the surface of the sheet-like member is wiped off with the first absorbent cotton, the sheet is made with the second absorbent cotton. 6. The method according to claim 5, further comprising the step of wiping again the surface of the member and putting the two absorbent cottons after wiping into a container, adding water to the container, and shaking the mixture for a predetermined time to obtain the extract. Drug contamination status inspection method.   From the time when the sheet-like member is installed at the inspection target location, the sheet-like member is collected after a predetermined period of time has elapsed, and information on the specimen captured on the surface of the sheet-like member within the period is obtained. A method for inspecting a contamination state of a medicine according to claim 5 or 6.   The drug according to any one of claims 5 to 7, wherein the drug is a chemical substance that can inhibit human health due to erroneous administration, exposure or environmental pollution, and can cause serious effects including death. Contamination status inspection method.   The method for inspecting a contamination state of a drug according to claim 8, wherein the chemical substance is a chemical substance classified into Group 1, Group 2A, and Group 2B by the International Organization for Research on Cancer.   The predetermined analysis means includes a liquid chromatograph / tandem mass spectrometer, high performance liquid chromatography, liquid chromatograph mass spectrometer, gas chromatography, gas chromatograph-mass spectrometer, gas chromatography / tandem mass spectrometer, inductively coupled plasma. The method for inspecting a contamination state of a drug according to any one of claims 5 to 9, which is a luminescence analyzer, an inductively coupled plasma mass spectrometer, a UV meter, or a fluorimeter.

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