01 course introduction.halogen. of alkaline metals
TRANSCRIPT
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LECTURE 1Theme: Course introduction and
importance of Pharmaceutical Chemistry
for pharmaceutical analysis. Introductionabout Pharmacopoeia and methods ofdrug analysis.
Inorganic drugs from group ofhalogenides of alkaline metals.
Associate prof. Mosula L.M.
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The plan1. A subject and the contents of pharmaceutical chemistry, its
interrelation with chemical, medical and biologic and
pharmaceutical disciplines.2. The State Pharmacopoeia of Ukraine (SPU), the International
(Ph. Int.), Europian (Ph. Eur.) and British Pharmacopoeias (BP),
and other analytical normative documentation (AND), which
regulates high quality of pharmaceutical preparations.
4. Classification of drugs.
5. Inorganic drugs from group of halogenides of alkaline metals:
obtaining, properties (appearance and solubility), identification,
tests, assay, storage, action and use of preparations of:
Fluorine (sodium fluoride);Chlorine (sodium and potassium chlorides);
Bromine (sodium and potassium bromides);
Iodine (sodium and potassium iodides).
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Pharmaceutical chemistry is a highly interdisciplinary sciencecombining organic chemistry with biochemistry, inorganic chemistry, analyticalchemistry, pharmacology, pharmacognosy, molecular biology and physical
chemistry.Pharmaceutical chemistry is the chemistry of drugs and
pharmaceutical products.
The aim of pharmaceutical chemistry is the discovery anddevelopment of new therapeutic agents.
The mission of the Pharmaceutical Chemistry course is tointroduce the structure, properties, and analysis (both qualitative andquantitative) of pharmaceutical agents as well as the fundamental techniquesused for near patient testing in clinical laboratories to the students. Topicsinclude some of the basic concepts in pharmaceutical chemistry as well as
methods of pharmaceutical analysis such as 1) the drug synthesis, 2) review oforganic functional groups found in drug molecules as well as cations and anionsof the inorganic drugs, 3) physicochemical properties related to drug action, 4)physicochemical and chemical analysis of drugs, 5) methods of identification ofpharmaceutical agents, 6) the storage conditions and use of drugs.
http://en.wikipedia.org/wiki/Organic_chemistryhttp://en.wikipedia.org/wiki/Biochemistryhttp://en.wikipedia.org/wiki/Computational_chemistryhttp://en.wikipedia.org/wiki/Pharmacologyhttp://en.wikipedia.org/wiki/Pharmacognosyhttp://en.wikipedia.org/wiki/Molecular_biologyhttp://en.wikipedia.org/wiki/Physical_chemistryhttp://en.wikipedia.org/wiki/Physical_chemistryhttp://en.wikipedia.org/wiki/Physical_chemistryhttp://en.wikipedia.org/wiki/Physical_chemistryhttp://en.wikipedia.org/wiki/Molecular_biologyhttp://en.wikipedia.org/wiki/Pharmacognosyhttp://en.wikipedia.org/wiki/Pharmacologyhttp://en.wikipedia.org/wiki/Computational_chemistryhttp://en.wikipedia.org/wiki/Computational_chemistryhttp://en.wikipedia.org/wiki/Biochemistryhttp://en.wikipedia.org/wiki/Organic_chemistry -
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Pharmaceutical Chemistry is a multifaceted discipline that
encompasses synthetic organic chemistry, inorganic, analytical,
physical, colloidal, biological chemistry and some disciplines of
medical and biological profile: biology, normal and pathologicalphysiology, microbiology. The pharmaceutical chemistry is closely
connected with other profile disciplines: pharmacognosy, technology
of medicines, the organisation and pharmacy economy,
pharmacotherapy.
Pharmaceutical chemistry is a discipline at the intersection of
chemistry andpharmacology involved with designing, synthesizing
and developingpharmaceuticaldrugs.
Compounds used as medicines are overwhelmingly organic
compounds including small organic molecules and biopolymers.
However, inorganic compounds and metal-containing compounds
have been found to be useful as drugs.
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Pharmacopoeiain its modern technical sense, is a book containingdirections for the identification of samples and the preparation of compoundmedicines, and published by the authority of a government or a medical orpharmaceutical society.The word derives fromAncient Greek (pharmakopoieia),from -(pharmako-) 'drug', followed by the verb-stem -(poie-)'make' and finally the abstract noun ending - (-ia). These three elementstogether can be rendered as 'drug-mak-ing'.
The aim of theInternational Pharmacopoeia (Ph. Int.), which is issuedby the World Health Organization as a recommendation, is to achieve a wideglobal uniformity of quality specifications for selected pharmaceutical products,excipients, and dosage forms. The information published in the InternationalPharmacopoeiais collated via a consultative procedure and is based on
international experience, the monographs being established in an independentmanner. Priority is given to medicines that are widely used throughout theworld. High priority is accorded to medicines that are important to WHO healthprograms, and which may not appear in any other pharmacopoeias.
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The European Pharmacopoeia (Ph. Eur.) of the Council of Europe is apharmacopoeia, listing a wide range ofactive substances and excipients used toprepare pharmaceutical products in Europe[citation needed]. The 2005 editionincludes 1800 specific and general monographs, including various chemical
substances, antibiotics, biological substances. The European Pharmacopoeia isdeveloped by the European Directorate for the Quality of Medicines (EDQM) andis a part of the Council of Europe, Strasbourg, France. It has been created by theConvention on the elaboration of a European Pharmacopoeiafrom 1964.
The British Pharmacopoeia(BP)is an annual published collection of qualitystandards for UKmedicinal substances. It is used by individuals andorganizations involved in pharmaceutical research, development, manufactureand testing. Pharmacopoeial standards are publicly available and legallyenforceable standards of quality for medicinal products and their constituents.The Pharmacopoeia is an important statutory component in the control of
medicines which complements and assists the licensing and inspection processesof the Medicines and Healthcare products Regulatory Agency (MHRA) of theUnited Kingdom. Pharmacopoeial standards are compliance requirements; thatis, they provide the means for an independent judgment as to the overall qualityof an article and apply throughout the shelf-life of a product. Inclusion of asubstance in a pharmacopoeia does not indicate that it is either safe or effective
for the treatment of any disease.
http://en.wikipedia.org/wiki/Council_of_Europehttp://en.wikipedia.org/wiki/Pharmacopoeiahttp://en.wikipedia.org/wiki/Active_substancehttp://en.wikipedia.org/wiki/Excipientshttp://en.wikipedia.org/wiki/Pharmaceuticalhttp://en.wikipedia.org/wiki/Europehttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Monographhttp://en.wikipedia.org/wiki/Antibioticshttp://en.wikipedia.org/wiki/European_Directorate_for_the_Quality_of_Medicineshttp://en.wikipedia.org/wiki/Council_of_Europehttp://en.wikipedia.org/wiki/Strasbourghttp://en.wikipedia.org/wiki/United_Kingdomhttp://en.wikipedia.org/wiki/Medicinalhttp://en.wikipedia.org/wiki/Pharmacopoeiahttp://en.wikipedia.org/wiki/Medicines_and_Healthcare_products_Regulatory_Agencyhttp://en.wikipedia.org/wiki/Medicines_and_Healthcare_products_Regulatory_Agencyhttp://en.wikipedia.org/wiki/Pharmacopoeiahttp://en.wikipedia.org/wiki/Medicinalhttp://en.wikipedia.org/wiki/United_Kingdomhttp://en.wikipedia.org/wiki/Strasbourghttp://en.wikipedia.org/wiki/Council_of_Europehttp://en.wikipedia.org/wiki/European_Directorate_for_the_Quality_of_Medicineshttp://en.wikipedia.org/wiki/Antibioticshttp://en.wikipedia.org/wiki/Monographhttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Europehttp://en.wikipedia.org/wiki/Pharmaceuticalhttp://en.wikipedia.org/wiki/Excipientshttp://en.wikipedia.org/wiki/Active_substancehttp://en.wikipedia.org/wiki/Pharmacopoeiahttp://en.wikipedia.org/wiki/Council_of_Europe -
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The State Pharmacopoeia of Ukraine (SPU) is a legal
document which contains the general requirements to
pharmaceutical preparations, monographies (pharmaceutical
articles) as well as techniques of quality assurance of medicalproducts. The first edition of SPU was published in 2001. It has
legislative character and its requirements are obligatory for all
enterprises and establishments, independently on a form of property
which develop, keep, supervise, realize and apply medical products.
Quality assurance of drugs in Ukraine at the state level is
carried out by Ministry of Public Health. It supervises the service of
medical products and products of medical appointment, the State
Enterprise Scientific and Expert Pharmacopoeial Centre, the StatePharmacological Centre, the State Drugs inspection (its structure
includes the Central laboratory of quality assurance of medical
products), territorial inspections of quality assurance of medical
products.
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Destructive impur ities
Impurities can be destructive when they obstruct the working nature of
the material. Examples include ash and debris in metals and leaf pieces
in blank white papers. The removal of impurities is usually donechemically. For example, in the manufacturing ofiron, calcium carbonate
is added to theblast furnace to remove silicon dioxide from the iron ore.
Zone refining is an economically important method for the purification
of semiconductors.However, some kinds of impurities can be removed by physical means. A
mixture of water and salt can be separated by distillation, with water as
the distillate and salt as the solid residue. Impurities are usually
physically removed from liquids and gases. Removal of sand particles
from metal ore is one example with solids.
No matter what method is used, it is usually impossible to separate an
impurity completely from a material. What technicians can do is to
increase the purity of a material to as near 100% as possible or
economically feasible.
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There are two types of impurities: generaland specific.The sources of general impurities are equipment, solvents, auxiliary
materials, and ofspecific onesby-products, semiproducts of synthesis of
substances of medicinal forms and compounds which are formed in medical
products at their wrong storage.The State Pharmacopoeia of Ukraine, other Analytical Normative
Documentation (AND) on the basis of experimental researches regulate
specific impurities and their quantity for each preparation.
For revealing the impurities in the medical products and their approximate
quantitative estimation use standard solutions (standards).Standard solution is a chemical term which describes a solution of
known concentration of testing impurity. The concentration of the solution
is normally expressed in unit ofppm (parts-per-million, ppm = 106) (One
part permillion (ppm) denotes one part per 1,000,000 parts, one part in 106,
and a value of 1 106.). For standards (standard solutions)preparationuse chemically pure initial substances (mother substances).
Presence of impurities defines by means of such methods:nephelometry
and colorimetry.
At the revealing same impurities use instrumental methods of analysis (atomic
absorption spectroscopy, spectrophotometry, chromatography, etc.).
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The proposed program will you prepare to fully and
confidently participate in health and biomedical careers.
Pharmaceutical companies need employees with strong
skills in modern chemical techniques as well as a good
understanding of biomedical issues such as drug action, drug design
and drug development. Students are increasingly careeroriented and
are motivated by early exposure to applications of their studies.
Pharmacists are health professionals who practice the
science ofpharmacy. It is very important propfession.
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Browse: British Pharmacopoeia 2009SPU, add. 1
Sodium ChlorideGeneral Notices
(Ph Eur monograph 0193)
NaCl58.44
DEFINITION
Content99.0 per cent to 100.5 per cent (dried substance).
CHARACTERS
Appearance
White or almost white, crystalline powder or colourless crystals or white or almostwhitepearls.
SolubilityFreely soluble in water, practically insoluble in anhydrous ethanol.
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OBTAINING:1. From water of lakes and the seas by evaporation.
2. Clarification of technical mineral salt NaCl from impurity, which
carry out consistently. Addition of a solution barium chlorideCl2 is precipitates by sulphates and phosphates:
Precipitate filter off, and to filtrate add excess of Na2CO3 forprecipitation of impurities of Mg, Ca, Ba salts.
For deleting of exess of Na2CO3 to filtrate add HCl:Na2CO3 + 2HCl = 2NaCl + H2O + CO2
SO42
+ Ba2+
BaSO4
HPO42
+ Ba2+
BaHPO4
Mg2+
+ CO32
MgCO3
Ca2+
+ CO32
CaCO3
Ba2+ + CO32 BaCO3
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IDENTIFICATION
A. It gives the reactions of chlorides(2.3.1).
Chlorides:A. (BrPh, SPU, add. 1). Reaction with solution of
AgNO3 in the nitric-acid medium.Dissolve in 2 ml ofwater R a quantity of the substance to be examined
equivalent to about 2 mg of chloride (Cl) or use 2 ml of the prescribed solution.
Acidify with dilute nitric acid R and add 0.4 ml ofsilver nitrate solution R1.Shake and allow to stand. A curdled, white precipitate is formed. Centrifuge and
wash the precipitate with three quantities, each of 1 ml, ofwater R. Carry out this
operation rapidly in subdued light, disregarding the fact that the supernatant
solution may not become perfectly clear. Suspend the precipitate in 2 ml ofwater
R and add 1.5 ml ofammonia R. The precipitate dissolves easily with thepossible exception of a few large particles which dissolve slowly.
NaCl + AgNO3 AgCl +NaNO3;
Cl+ Ag+ AgCl
curdled, white precipitate
AgCl + 2NH4OH [Ag(NH3)2]Cl + 2H2O
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B. (BrPh, SPU, add. 1).Reaction with oxidizers inthe acid medium with the next identification of toxic gas
Cl2.Introduce into a test-tube a quantity of the substance to be examined equivalent toabout 15 mg of chloride (Cl) or the prescribed quantity. Add 0.2 g ofpotassiumdichromate Rand 1 ml ofsulphuric acid R. Place a filter-paper strip impregnated with0.1 ml ofdiphenylcarbazide solution Rover the opening of the test-tube. The paperturns violet-red. The impregnated paper must not come into contact with the potassiumdichromate.
6NaCl + K2Cr2O7 + 7H2SO4 = 3Cl2 + Cr2(SO4)3 + K2SO4 + 3Na2SO4 + 7H2OCr2O72 + 14H+ + 6 2Cr3+ + 72
2Cl 2 Cl2
diphenylcarbazide diphenylcarbazonediphenylcarbadiazone
(colourless) (orange-yellow) (violet-red)
O C
NH NH C6H
5
NH NH C6H5
CL2
O C
N N C6H5
NH NH C6H5
CL2
O C
N N C6H5
N NC
6H
5
-2 HCl
-2 HCl
+ +
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B. It gives the reactions of sodium(2.3.1).Sodium and Sodium Salts:
A. (BrPh, SPU, add. 1).Reaction with potassium pyroantimonate
solution.
Dissolve 0.1 g of the substance to be examined in 2 ml ofwater R or use 2 ml of theprescribed solution. Add 2 ml of a 150 g/l solution ofpotassium carbonate R and
heat to boiling. No precipitate is formed. Add 4 ml ofpotassium pyroantimonate
solution R and heat to boiling. Allow to cool in iced water and if necessary rub the
inside of the test-tube with a glass rod. A dense white precipitate is formed.
NaCl + K[Sb(OH)6] Na[Sb(OH)6] + KClNa+ + [Sb(OH)6] Na[Sb(OH)6]
dense white precipitate
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B. Reaction with methoxyphenylacetic reagent.Dissolve a quantity of the substance to be examined equivalent to about 2 mg of sodium
(Na+) in 0.5 ml ofwater R or use 0.5 ml of the prescribed solution. Add 1.5 ml of
methoxyphenylacetic reagent R (it is solution ofmethoxyphenylacetic acid in the
tetramethylammonium hydroxide solution and ethanol) and cool in ice-water for 30
min. A voluminous, white, crystalline precipitate is formed. Place in water at 20 C
and stir for 5 min. The precipitate does not disappear. Add 1 ml ofdilute ammonia
R1. The precipitate dissolves completely. Add 1 ml ofammonium carbonate solution
R. No precipitate is formed.
white, crystalline precipitate
Other reaction:
SPU, N. Pyrochemical reaction.Sodium salt, wetted with hydrochloric acid
and brought in a colourless flame, paints its in yellow colour:
Na+ + h *Na+ Na+ + h1.
CH
O
C
O
OHCH3
CH3
4
NOH CH
O
C
O
CH3 ON(CH
3)4
+
CH
O
C
O
O
CH3
CH
O
C
O
CH3
Na
ONa
+ +
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ASSAY
(BrPh, SPU, add. 1). Argentometry, direct titration
with potentiometric fixation of end-point.Dissolve 50.0 mg in water R and dilute to 50 ml with the same
solvent. Titrate with 0.1 M silver nitrate determining the end-point
potentiometrically (2.2.20).
1 ml of0.1 M silver nitrate is equivalent to 5.844 mg of NaCl.NaCl + AgNO3 = AgCl + NaNO3
m(NaCl) = M. m.
Other methods:1.SPU, add. 1. Thiocyanatometry.
2. SP X. Argentometry, direct titration (Morh method).Indicator K2CrO4.3. Argentometry, back titration (Volhard method) (see thiocyanatometry). Toinvestigated solution add double excess of standart solution of AgNO3.
NaCl + AgNO3 = AgCl + NaNO3AgNO3 + NH4SCN = AgSCN + NH4NO3
3NH4SCN + (NH4)Fe(SO4)2 = Fe(SCN)3 + 2(NH4)2SO4
m(NaCl) = M. .
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NaCl + AgNO3 = AgCl + NaNO3
m(NaCl) = M. .
2NaCl + g(NO3)2 = gCl2 + 2NaNO3
m(NaCl) = M. .
O C
N N C6H5
NH NH C6H
5
Hg(NO3)2 O C
N N
C6
H5
NH N
C6H
5
Hg
N
N
C6H
5
C6H
5
N
NH
C O HNO3
2 + + 2
Argentometry, direct titration (Fajance method).
Indicatorfluoresceine.
5. Mercurymetry, direct titration.
Indicatordiphenylcarbazone.
To titrate until changing of colouring solution from yellow-red to dark blue colour.
In the equivalence point excess drop of titrant g(NO3)2 interaction with indicator of
diphenylcarbazone and formation of dark blue complex.
Ley e ing
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Ley e ing where applicable, that the substance is suitable for use in the manufacture ofparenteral dosage forms; where applicable, that the substance is suitable for use in the manufacture ofperitoneal dialysis solutions, haemodialysis solutions or haemofiltration solutions.
Action and useUsed in treatment of electrolyte deficiency.Plasma substitute.Ions Na + are basic extracellular Ions. It is the basic component of all saltsolutions, which are applied as plasma substitutes.Isotonic (0,9 %) a solution of sodium chloride (Soluto Natr chlordsotonca pro
njectonbus) apply hypodermically, intravenously (more often drop method) and in clysteras antitoxic means and at organism dehydration, at bleedings, a shock (sometimes - to 3 L).Introduction of great volumes of this solution can lead chloride acidisis, hyperhydrations,
strengthening of conclusion of Potassium from an organism.
PreparationsCompound Glucose, Sodium Chloride and Sodium Citrate Oral SolutionOral Rehydration Salts
Potassium Chloride and Sodium Chloride Intravenous InfusionPotassium Chloride, Sodium Chloride and Glucose Intravenous InfusionSodium Chloride Eye DropsSodium Chloride Eye LotionSodium Chloride Intravenous InfusionSodium Chloride and Glucose Intravenous InfusionSodium Chloride Irrigation SolutionCompound Sodium Chloride MouthwashSodium Chloride Oral Solution
Sodium Chloride SolutionSodium Chloride Tablets
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Thanks for attention!