CA1229292A - Method for preparation of a unitary dry reagent containing heterogeneous chemicals - Google Patents

Method for preparation of a unitary dry reagent containing heterogeneous chemicals

Info

Publication number
CA1229292A
CA1229292A CA000461826A CA461826A CA1229292A CA 1229292 A CA1229292 A CA 1229292A CA 000461826 A CA000461826 A CA 000461826A CA 461826 A CA461826 A CA 461826A CA 1229292 A CA1229292 A CA 1229292A
Authority
CA
Canada
Prior art keywords
solid
reagent system
reagents
lithium hydroxide
suspension
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA000461826A
Other languages
French (fr)
Inventor
Richard B. Edwards
Robert L. Bodden
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Baxter International Inc
Original Assignee
Baxter Travenol Laboratories Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Baxter Travenol Laboratories Inc filed Critical Baxter Travenol Laboratories Inc
Application granted granted Critical
Publication of CA1229292A publication Critical patent/CA1229292A/en
Expired legal-status Critical Current

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/70Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving creatine or creatinine

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

ABSTRACT OF THE DISCLOSURE

The specification describes a method for the isolation of heterogeneous reagents by encapsulation of one or more of such reagents; a unitary solid reagent system prepared by the foregoing method; and a process for conducting an assay of biological fluid sample utilizing the foregoing reagent system.

Description

Method for Proportion of Q IJnitary Dry Regent System containing heterogeneous Chemicals BACKGROUND OF THE INVENTION

Field of the Invention: This invention is directed to a method, a composition of matter and a process. More specifically, the invention described hereinafter is directed to a method for the isolation of heterogeneous 10 reagents by encapsulation of one or more of such reagents; a unitary solid reagent system prepared by the foregoing method; and a process for conducting an assay of biological fluid sample utilizing the foregoing reagent system.

15 Description of Prior Art: In the field of clinical chemistry, the assay of a patient's body fluids has traditionally involved the addition GO certain reagents, in specific portions, to an Alcott OX patient's sample and thereafter monitoring the patient's sample for the presence of a reaction product whose concentration can be correlated to the analyze of interest. Because of 20 analytical instrument design, these reagents have generally taken the form ofliquids. Ordinarily, such reagents are sold in liquid form, or, if available in solid form, are reconstituted with fluid prior to their use. In the event that the reagent system employs two or more heterogeneous reagents, most often those reagents must be effectively isolated from one another to prevent their 25 premature interaction. Such interactions generally take the form of reduced shelf-life, and in extreme cases, in the rendering of one of the reagents ineffective for performance of a particular assay. One such reagent system which is susceptible to this type of interaction is used in the determination ofcreatinine levels via a Gaffe reaction. As is well know, the tough reaction 30 requires the use of an alkali hydroxide and an alkali salt of picnic acid in the performance of a creatinine assay. These two reagents react with one another in solution and, thus, any solution wormed from these materials is of:
limited stability. Generally, these reagents are isolated from one another until immediately prior to use and, even then, they are generally added to the 35 sample sequentially.

Page 2 Lo In typical commercially available automated systems which employ reagent systems ion performance ox creatinine assay via a Jiffy reaction, the reagents, notably the allele hydroxide and picnic acid or pirate salt, are initially isolated Iron one another by storage in separate containers. If there were a failure to take such preventative measures, it would result in the type of instability alluded to previously. In the Abbott ABA 100 clinical analyzer, and the Dupont ALA Clinical Analyzer, the allele hydroxide and picnic acid solutions are prepared as two separate liquids and these liquids stored in separate dispensing stations, thus requiring coordination of handling and precision on-site mixing. Once these two solutions are combined, their shelf life is limited, generally less than 14 days. In the Technic on SUMAC Clinical Analyzer, three (3) separate liquids are used for performance of a creatinine assay via Jiffy reaction. This introduces a further variable into the system.

All of the foregoing clinical systems described hereinabove require careful monitoring in order to insure that the reagents are still active; and, that precise calibration of the dispensing mechanism for delivery of required amounts is achieved.

The introduction of solid reagent systems for clinical assay has at-tempted to address the problems and inconveniences with liquid based reagent systems described hereinabove. Typically, where such reagent systems were composed of heterogeneous r reagents, separate tablets, each one containing one of the heterogeneous reagents would be required to ensure stability of the reagent systems. These solid reagents were generally more stable than comparable liquid systems; however, they have up to now been incompatible with assays requiring the presence of heterogeneous reagents in a unitary solid. Thus, current analytical systems requiring the use of heterogeneous reagents in a solid form also suffer from shortcomings of their similar liquid counterparts. Where solid reagent systems are used, they require the solid be reconstituted as a liquid prior to performance of the assay. The need to reconstitute the solids as liquids which must then be mixed in certain proportions introduces the potential for variability into the assay as mentioned above.

Page 3 ~2~3~

One possible alternative ion elimination of human error and the variability which flows from such manipulation would be to have all reagents remeasured in a single granular or tabulated form. The reagent could then be simply introduced in thy reaction vessel either prior to or subsequent to delineate, followed by dissolution and the addition of patient sample. Under certain conditions, the sample itself may serve as the delineate. This system would eliminate or reduce the potential for variability in measurement and/or dispensing of reagents and, thus, increase the reliability and repeatability.

An automatic clinical analyzer of advanced design which is adapted to make use of a unitary dry reagent system is the PARAMAX Automated Clinical Analyzer developed by American Dade Division of American Hospital Supply Corporation. The PORKS instrument system (to be commercially available around January 1, 1984) uses a tabulated reagent for the performance of clinical assays on patient's samples. The specifications of tabulated reagents used in this system are that they must be stable up to six (6) months; capable of dispensation from a container of a type described in copending3 commonly assigned Canadian Patent application 407,~11, filed July 20, 1982; and be capable of rapid dissolution to form an optically clear solution. In all but one of the 32 reagent systems described for the PARAMAX instrument to date, virtually all reagents for the performance of a specific assay are incorporated within a single tablet. The simplicity and advantages of such a system are immediately apparent. Because of the specifications for such a tabulated reagent for the PARAMAX analyzer, the use of hotter-generous constituents presented a rather unique set of problems. For example could heterogeneous chemicals be incorporated within a unitary solid, compacted in tabulated form and still be capable of rapid dissolution to form antiquely clear reagent solution? Because of the uniqueness of the PARAMAX system, these problems have not, up to now, been addressed. Where these problems had been confronted in the past, the traditional approach was to modify the instrument to accommodate the limitations of the reagents. Because this traditional approach was unacceptable to designers of the PORKS instrument, new techniques had to be developed to accommodate such heterogeneous chemicals in a unitary solid.

Pave I
.

OI~ECTS OF Tile INVENTION

Accordingly, the object of this invention is to remedy the above as well as related deficiencies in the prior art.

More specifically, it is the principal object of this invention to provide a method for the preparation of a unitary, solid reagent system containing heterogeneous ingredients or reactants for use in a luff reaction system.

It is another object of this invention to provide a unitary, solid reagent system containing heterogeneous ingredients in which each ingredient is in precise relationship to other ingredients also contained within the solid.
It is yet a further object of this invention to provide a dry tabulated reagent system in which a pair of heterogeneous reagents are separated from one another by encapsulation of one or both such reagents.

It is still yet another object of this invention to provide a simplified technique for conductillg a clinical chemistry assay utilizing a unitary dry tabulated reagent system.

SUMMARY OF THE INVENTION

The above and related objects are achieved by providing a method or preparation of a unitary dry solid prom a heterogeneous reagent system. The method of this invention can be exemplified with the reagents which are used in the conduct of the creatinine assay via a afire reaction. In the preparation of a solid reagent system Ion a creatinine assay via a gaffe reaction, an alkali salt of picnic acid is isolated in a solid form. Similarly, lithium hydroxide is isolated in the solid Norm. For the purpose of this disclosure, the phrase "solid reagent system" is inclusive ox not only the reactive components of the solid but also tabulating aids it bulking agents, lubricants and the like). Either one ox the Foregoing reagents is thereafter coated with an encapsulation effective amount of an agent which is otherwise compatible with the physical specifications ox the solid (i.e., tablet) and the cherllical constituent of the sample to be annulled. Typically, this agent can r'~gc 5 be another reagent of the reagent system which is inert relative to the encapsulated component; or a bulking agent used in the formation of the solid; or a combination of reagent and bulking agent. The purpose and extent of such encapsulation is to effectively isolate the encapsulated material and thereby prevent its premature interaction with another of the reagents used in the conduct of the particular assay. Subsequent to the encapsulation procedure, various reagents, including the encapsulated material, are come brined in the relative proportions into a unitary solid form. The solid can takethe form of free flowing material (i.e., powder or granule) or be compressed in a tablet of precise dimension and weight.

DESCRIPTION OF THE INVENTION
INCLUDING PREFERRED EMBODIMENTS

This invention describes a method for preparing a stabilized dry reagent system for use in bioassay requiring the isolation of one or more dry components to prevent their premature interaction. A representative fee-gent system requiring isolation of their key chemical component from one another are the chemical constituents used in the gaffe analytical protocol for creatinine determination. In brief, the gaffe analytical protocol involves the following reaction:
2,4,6-trinitrophenol -I creatinine eXceS~adduct L ion adduce = a :~anowsky-type adduce (a colored complex of pirate creatinine) Following or concurrent with interaction of the above reagents and sample, the absorption of the solution is monitored by conventional spectra-photometry at a predetermined wavelength. It has been observed experiment tally that picnic acid and lithium hydroxide interact with one another to an extent proportional to reactants concentration and temperature. The soul-lion of pirate and lithium hydroxide containing both these reagents is stable or only a relatively short period of time; thus, these two reagents must be maintained apart from one another until combined, at the appropriate phase of the analytical procedure, in the presence of the patient sample. The basic 2~2 tendency ox these two (2) components of the gaffe reagent system to interact is also prevalent when they are combined with one another in the solid form.
Their interaction is manifested as abbreviated stability or shell file of the solid. This invention permits the formation ox such unitary dry reagent system into a stable solid composition prom a complement of interactive (hereinafter "heterogeneous") reagents.

As applied to the Joy reagent system, the procedure involves provide in an alkali salt of picnic acid in solid form as one of the reagents.
Subsequently, lithium hydroxide, also in solid form, is twice-coated with an encapsulating agent. This agent can preferably be any non polymeric bonding agent compatible with a tabulated system, i.e., one which retains its optical clarity in reconstituted solution, permits a rapid dissolution capability; and, which is non-reactive in the solid Norm with respect to the other components in the reaction system. This initial encapsulation process can be Hollowed, in one ox the preferred embodiments of this invention, by further encapsulation sequence with a detergent/surIactant. The above encapsulation procedure effectively prevents the interaction of the lithium hydroxide it the pirate when placed in a unitary solid state. After encapsulation of the lithium hydroxide, the pirate salt and the coated lithium hydroxide can -then be combined. Formulation of a unitary dry solid in the foregoing manner will maintain the stability of the reagent system by preventing their interaction, while retaining the requisite optical clarity of the reconstituted solution.
Alternatively, this procedure is equally applicable to isolation of the pirate salt by coating it rather than the lithium hydroxide.

In this particular application, sucrose is used as a bulking agent for tabulating purposes. Picnic acid must be neutralized by forming the alkali salt so as to prevent the acid catalyzed hydrolysis of the sucrose to produce glucose and f fructose. The picnic acid normally acts as a catalyst for this reaction, both in aqueous solution end the solid phase. Glucose is a substance Welch interferes with the luff reaction and the elimination of this is accomplished by using the neutralized pirate. The alkali salt of picnic acid can be Wormed by introducing lithium hydroxide to an aqueous solution ox picnic acid, followed by the addition ox sucrose to the pirate solution and subsequent lyophilization ox the resultant mixture. The lyophilization step is preferably conducted in stainless steel or glass trays since the pirate age solution is reactive towards certain materials (i.e., reacts with aluminum to produce intensely red product).

Coated lithium hydroxide can be obtained by preparing a solution of lithium hydroxide in isopropanol and to the stirred solution is added an aqueous solution of sucrose. Adding sucrose drops, by fine spraying throughout the bulk of the suspension, or any other metered controlled - 10 addition technique is acceptable so long as the even distribution ox sucrose solution throughout the lithium hydroxide is accomplished. Because the sucrose is not soluble in isopropanol, it crystallizes out using the lithium hydroxide particles as nuclei around which to grow, hence the coating of lithium hydroxide. The resulting product is washed, dried and sieved in preparation ion a second layer of sucrose to be applied by the same procedure. A spray-drying apparatus can be employed to effect the controlled addition of sucrose wherein the solid lithium hydroxide is suspended by air currents in a spray-drying chamber and an aqueous solution of the appropriate solute is sprayed into the chamber at a controlled rate and droplet size. This results in the condensation of the sucrose around the lithium hydroxide, and the product is Hollowed by rapid drying.

In a similar manner, the encapsulated lithium hydroxide can be added to warmed methanol and to the suspension which is formed is added dodecyl sodium sulfate (hereinafter "SDS"), followed by evaporation ox the methanol leaving the product which is then dried and sieved. the SDS is an ionic detergent that reduces protein interference during the luff reaction, and acts as a clarifying agent keeping the protein in solution. Furthermore, the SDS acts as a lubricant and mold-releasing amen t reducing the amount of sticking of the mixture to the equipment used in the tabulating process.

The tablet can be formed from this free-flowing solid material prepared by the above manner, blending the Iyophilized pirate and coated lithium hydroxide with sucrose or similar substance (as a bulking agent) in the proper relative proportions followed by a compression of the blend into wafers which are then granulated and tabulated.

Pow I

This procedure can be adapted to any reagent system which contains two or more hetero~encous reagents which must be kept isolated Iron one another during storage. An example of another such reagent system are the heterogeneous chemicals used to measure magnesium levels in blood serum.
In the analytical protocol Ion magnesium quantitation Calrnagite (available from Eastman Chemicals, Tennessee, which has the generic name of lo hydroxy-4-rnethyl 2-phenylaza)-2-napthal-4-sulionic acid), in an excess alga-line environment, reacts to yield a colored complex which can be spectropho-to metrically measured. In this procedure, the alkaline reagent used is tribasic sodium phosphate. The problem with this reagent is that it has the tendency to absorb water, which decreases the linearity of measurements observed and also decreases the reagent system stability.
By coating the sodium phosphate with manna lot or some such similar bulking agent, the hydroscopic tendency of this alkaline reagent is reduced, thereby the reagent system can be contained in a single unitary dry solid for use in an automatic chemical analyzer.
EXPELS

The Examples which follow further describe, define and illustrate a number of different embodiments of this invention. The apparatus and techniques used in the conduct of this method, in the evaluation of the unitary dry systems produced thereby, are standard of hereinabove described.
Par is and percentages appearing in such Examples are by weight unless otherwise indicated.

Example l The procedure for manufacturing a single solid reagent involves three basic steps:

1. ration of a Iyophilized lithium pirate Prepare a lithium pirate solution by adding 62g of AWAKES. grade picnic acid (85%) to nine (9) liters of water at room temperature.
Add 6.61g of lithium hydroxide to this with mixing, until a homogeneous solution results. Dissolve 463g sucrose in the pirate solution and bring the volume to ten (10) liters by adding 1 0 water.

Loopholes the liquid reagent in stainless steel trays.

Sieve the resulting product through a 40 mesh (US. standard) stainless steel sieve and collect it.

2. Preparation of coated-lithium hydroxide Suspend 65g of lithium hydroxide in 1000 ml of isopropanol, while stirring vigorously and keeping at a temperature of 40- 50C.
- Prepare a sucrose solution by dissolving 26g of sucrose in 45 ml of warm water, added drops to the above suspension, while stirring. Collect the precipitated product by vacuum filtration washing with isopropanol, and dry. Sieve this product through a I mesh stainless steel screen and continue with the second layer of sucrose in the same manner described above, using ~6g sucrose-coated lithium hydroxide with a solution- of 24g of sucrose in 40 ml water. Add 1 08.6g of dried sucrose-double-coated lithium hydroxide (about 54% w/w lithium hydroxide to 1000 ml warmed methanol; add to this suspension 108~3g powdered dodecyl sulfate (SDS). Stir the mixture vigorously in a suitable mixer (e.g., Hubert "ICitchen aide") until all the methanol has evaporated. Dry and sieve the product through a 40 mesh stainless steel screen.

--I Page 10 owe C3,~
3. reparation of Final tablet Ed reagent Combine 462.2g sieved, sucrose-lithium pirate mixture with 196.6g of the sieved triple-coated lithium hydroxide and 341.2g of 40 mesh screened and dried sucrose. Blend in a twin shell blender -for about 45 minutes.

Compress the blend into 1.27 cm diameter waxers, granulate through a 20 mesh screen and tablet the granules into 0.397 cm diameter flat face tablets.

NOTE: Quantities described include calculated excesses to compensate for processing losses.

Example 2 Lithium pirate is prepared as described in Example 1. To prepare the coated lithium hydroxide, suspend 65g of lithium hydroxide in 1000 ml of isopropanol, while stirring vigorously at a temperature ox 40-50C. Prepare a minutely solution by dissolving 26g minutely in 45 ml of warmed water and adding drops to the suspension, while stirring. Collect the precipitated product by vacuum filtration, wash with isopropanol and dry. Sieve this product through a 40 mesh stainless steel screen and continue with a second layer of minutely in the same manner described above, using ~6g minutely-coated lithium hydroxide with a solution of 24g minutely in 40 ml of water.

Add 108.6g of dried minutely double-coated (54% w/w lithium hydrox-ides to 1000 ml warmed methanol; add to the solution 10~.3g powdered SDS.
Stir the mixture vigorously in a suitable mixture until all the methanol has evaporated. Dry and sieve the product through a 40 mesh stainless steel screen. Form the tablet by blending and slugging two components as described above.

Lo Example 3 Aster the lithium pirate is prepared, a solution ox orbital is used to double-coat the lithium hydroxide followed by coating SDS and tabietting the blended mixture using the method and proportions as described in Example 1.

Claims (8)

WHAT IS CLAIMED IS
1. A method for preparing a stabilized dry solid reagent from hetero-geneous reagents for creatinine assay via a Jaffe reaction, comprising:

(a) providing an alkali salt of picric acid in solid form;

(b) providing lithium hydroxide in solid form;

(c) coating at least one of said picric acid salt or lithium hydroxide by forming a suspension of one of said components in a nona-queous liquid and then adding to said suspension an aqueous solution of a compatible component of said solid reagent system whereby said component is precipitated upon the suspended parti-cles and thereby effectively isolates said particle from interac-tion in the solid state with the other components of the reaction system.

(d) isolating the coated component of the reagent system; and (e) combining the isolated coated component of said reagent system with the other constituents of the Jaffe system in the appropriate relative proportions into a unitary solid.
2. The method of claim 1, wherein the aqueous solution is contacted with the nonaqueous suspension by spraying said solution into the suspension.
3. The method of claim 1, wherein the aqueous solution is contacted with the nonaqueous suspension by spraying said solution onto the suspension.
4. The method of claim 1, wherein:

(a) either the solid lithium hydroxide or alkali salt of picric acid is suspended by air currents in a spray drying apparatus chamber;
and (b) the aqueous solution is sprayed into said chamber at a predetermined rate and droplet size such that said aqueous solution contacts said suspended solid and condenses thereon;
5. The method of claim 1, wherein the coating compound is a nonpoly-meric substance that does not interfere with the reaction system.
6. A process for performance of analysis of an aqueous sample for the presence of an analyte in an automated clinical analyzer, comprising.

(a) providing a stabilized dry solid reagent system containing hetero-geneous reagents in tablet or granular form, wherein at least one of said heterogeneous reagents is coated with an encapsulation effective amount of another of the compatible components of the reagent system;

(b) adding said solid reagent system and a solvent for said solid to a reaction vessel;

(c) dissolving said solid reagent system in said solvent in the reaction vessel;

(d) adding to the reaction vessel a sample containing an unknown concentration of creatinine; and (e) monitoring said reaction vessel for the presence of a colored constituent which can be correlated with creatinine concentration of the sample.
7. The process of claim 6, wherein sufficient ultrasonic energy is applied to the solid reagent system to effect its rapid dissolution in the solvent.
8. The method of claim 6, wherein:

(a) the analyte is creatinine; and (b) the solid reagent system in comprised of lithium hydroxide and an alkali salt of picric acid such that either or both components are isolated from one another.
CA000461826A 1983-08-26 1984-08-24 Method for preparation of a unitary dry reagent containing heterogeneous chemicals Expired CA1229292A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US52764083A 1983-08-26 1983-08-26
US527,640 1983-08-26

Publications (1)

Publication Number Publication Date
CA1229292A true CA1229292A (en) 1987-11-17

Family

ID=24102327

Family Applications (1)

Application Number Title Priority Date Filing Date
CA000461826A Expired CA1229292A (en) 1983-08-26 1984-08-24 Method for preparation of a unitary dry reagent containing heterogeneous chemicals

Country Status (4)

Country Link
EP (1) EP0153370A1 (en)
JP (1) JPS60502168A (en)
CA (1) CA1229292A (en)
WO (1) WO1985001107A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5086001A (en) * 1989-12-01 1992-02-04 Baxter International, Inc. Automated test method for evaluating the physical compatibility of intravenous drugs in solutions

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5464777A (en) * 1994-09-26 1995-11-07 Miles Inc. Dry reagent for creatinine assay

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA544029A (en) * 1957-07-23 H. Reman Gerrit Coating finely divided solid materials
DE1648977A1 (en) * 1967-07-20 1970-08-13 Merck Anlagen Gmbh Color reagent for the determination of creatinine
US3705013A (en) * 1970-01-05 1972-12-05 Xerox Corp Analytical procedures and compositions therefor
US3988010A (en) * 1975-02-20 1976-10-26 Monsanto Company Apparatus for the continuous agglomeration of aqueous latices
US4279691A (en) * 1979-12-12 1981-07-21 Matsushita Electric Industrial Co. Method of making boron cantilever

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5086001A (en) * 1989-12-01 1992-02-04 Baxter International, Inc. Automated test method for evaluating the physical compatibility of intravenous drugs in solutions
US5281396A (en) * 1989-12-01 1994-01-25 Baxter International Inc. Automated test system for evaluating the physical compatibility of intravenous drugs in solutions

Also Published As

Publication number Publication date
WO1985001107A1 (en) 1985-03-14
EP0153370A1 (en) 1985-09-04
JPS60502168A (en) 1985-12-12

Similar Documents

Publication Publication Date Title
Mezl et al. Properties and analysis of a stable derivative of pyrroline-5-car☐ ylic acid for use in metabolic studies
US3932943A (en) Method of preparation of lyophilized biological products
EP0641389B1 (en) Reagent compositions for analytical testing
US4615972A (en) Stabilization of indicators for detecting enzyme activity
CN100558344C (en) Solid formulation for dialysis and manufacture method thereof
CA2152413C (en) Dry reagent for creatinine assay
US5618562A (en) Spherical granule, production method thereof and medicinal preparation using said granule
US3997470A (en) Surfactant containing reagent formulations for assaying biological specimens and methods of preparing same
Hagen et al. Plasma and urinary oxalate and glycolate in healthy subjects
US3511607A (en) Laboratory reagent for assay of total bilirubin
US3600132A (en) Process for the determination of the hydroxyproline content of biological fluids,and diagnostic packs for this determination
CA1092035A (en) Liquid stabilized coenzyme
US3816262A (en) Reagent formulations for assaying biological specimens amd methods of preparing and using same
EP0928421B1 (en) Standard solution for the determination of thyroid function
CA1229292A (en) Method for preparation of a unitary dry reagent containing heterogeneous chemicals
US4712310A (en) Co-spray technique
US3119751A (en) Reagents and analysis of nitrogen
EP0717838A1 (en) Reagent and method of its use
Stead et al. Ibuprofen tablets: dissolution and bioavailability studies
Pedersen et al. Miconazole and miconazolenitrate chewing gum as drug delivery systems-a practical application of solid dispersion Technique
JPH0724061A (en) Prepation for hemodialysis
US3953295A (en) Reagent formulations for glucose assay
CN113278677B (en) Preparation method of alpha-amylase determination reagent ball, reagent ball and microfluidic chip
US4310624A (en) Stabilized liquid coenzyme compositions for diagnostic determinations
Ellerbe et al. The stability of uric acid in ammonium hydroxide.

Legal Events

Date Code Title Description
MKEX Expiry