Reviewer - Prelims Midterms.pdf

Quality Control 1 w/ D.T.A.

Prelims

2018 - 2019

References:

Ansel, H. (2010). Pharmaceutical Calculations (13th (13th ed.). Lippincott Williams & Wilkins. Cascabel, K. M. (2017). Quality Control and Quality Assurance. Module 6 - Quality Assurance/Quality Control . Harris, D. C. (2010). Quantitative Chemical Analysis (8th (8th ed.). New York, NY: W.H. Freeman and Company. Quantitative Pharmaceutical Chemistry. McGraw Knevel, A. M., & DiGangi, F. E. (1977). Jenkins' Quantitative Hill Inc. QUALITY: What is Quality? Totality of characteristics or features of a product that bears its capacity to satisfy stated or implied needs Determines degree of acceptability Sum total of the organized arrangement made with the object of ensuring that products will be consistently of the quality required by their intended use

Quality Assurance

Quality Control

QA Departmental Functions: ✓ Assures policies are followed inept to economic issues associated with manufacturing and distribution of the product ✓ Cooperate with regulatory agencies and final authority for product acceptance or rejection ✓ Helps to identify and prepare necessary SOPs relative to control of quality ✓ Audit and quality monitoring Part of the GMP concerned with sampling, specifications, testing, organization, documentation and release procedures QC Departmental Functions: ✓ Testing and Acceptance of only high-quality raw materials, representative samples ✓ IP tests against criteria ✓ Monitors environmental conditions ✓ Controls packaging components Three (3) Main Areas of QC: 1. Raw Material Quality Control (RMQC) 2. In Process Quality Control (IPQC) 3. Finished Produce Quality Control (FPQC) Document that specifies all the tests to be conducted on a product and/or appropriate references containing details of procedure and expected result Document with the result of all the tests conducted on the material, to show compliance or non compliance with the standard specifications This is a concise and precise statement of the ingredients that comprise the product, together with the percentage and/or weight of each This should enumerate the characteristics of all the materials that go into the product and the permissible range of purity of each ingredient

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Monograph Certificate of Analysis Formula Raw Material Specification Standard Operating Procedure (SOP) Finished Product Specification Sample

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This is a step by step method on how to go about a job This should cover all characteristics that affect the proper performance, purity, safety, and stability of the product Finite number of objectives selected from a batch

– Crucis, P. & Lapuz, A.M.

Joshua Mariano Jimenez


Prelims

2018 - 2019

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DEFECTS undesirable characteristic of a product; failure to conform to specifications (Cascabel, 2017) : Variable Defect Attribute Defect

Can be measured directly by instruments Cannot be measured directly by instruments

Critical Defect

May endanger life, property and may render the product non functional Example: absence of warning in a label f or a potent drug Renders the product useless Example: crack in a syrup bottle Does not endanger life, property nor will it affect the function, but nevertheless remains a defect, since it is outside the prescribed limits Example: slight deviation of the color of the label from the color standards

Major Defect Minor Defect

Ocular Defect Internal Defect Performance Defect

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Visible defects Example: foreign particulate contamination Not seen, although present Example: subpotent drug product Defect in function Example: suppository that does not melt at body temperature

Sources of Variation Source of Variation Materials

Machines

Methods

Men

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Examples Between suppliers of same substance Between batches from same supplier Variation within a batch Variation of equipment for the same process Difference in adjustment of equipment Aging and improper care Inexact procedures Inadequate procedures Negligence by chance Improper working conditions Inadequate training and understanding Dishonesty, fatigue and carelessness




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Prelims

2018 - 2019

aka Volumetric Analysis an analytical method, in which the volume of a solution of known concentration consumed during an analysis is taken as a measure of the amount of active constituent in a sample being analyzed

Analyte Endpoint Equivalence Point Equivalent (Equiv, Eq)

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Gram equivalent weight (GEW)

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The chemical substance/s being analyzed; also active constituents The actual point in which the titration is stopped due to the sudden change in some property of the reaction mixture The theoretic point at which equivalent amounts of a titrant and analyte have reacted

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(Equiv; Eq) The number of gram equivalents involved in a quantitative procedure

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The gram equivalent of a chemical; weight in grams which is chemically equivalent to 1 gram atom of hydrogen (1.0079g) For neutralization reactions, it is defines as that weight of a substance in grams which (1) contains, (2) furnishes, (3) reacts with, directly or indirectly), or (4) replaces a 1 gram atom of ion of hydrogen

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Gram milliequivalent weight (GmEW)

Defined as GEW/1000

Indicator

A chemical which changes color at or very near the point in the titration where equivalent quantities of analyte and titrant have reacted

Milliequivalent (mEq)

The number of gram milliequivalents involved in a quantitative procedure

Molarity (M) Normality (N) Primary Standard Secondary Standard Standard Solution Standardization Stoichiometric Point Titer Titrant Titration

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An expression of concentration expressed as mole of solute per liter of solution (mol/L) The number of equivalents of solute per liter (Eq/L) or milliequivalent per milliliter (mEq/mL) of a solution A carefully weighed sample of a substance of known purity The use of standard solution with known concentration to standardize another solution A solution of known normality of molarity The determination of the normality or molarity of a solution See Equivalence Point

The weight of a substance chemically equivalent to 1mL of a standard solution A solution known concentration usually added by means of a buret The act of adding and measuring the volume of titrant used in an assay

Types of Volumetric Apparatus: 1. TD to deliver 2. TC to contain Types of Cleaning Solutions for Glassware: 1. Na2Cr2O7 in H2SO4 2. Trisodium phosphate solution 3. Solution of synthetic detergent best cleaning agent to use

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Method of Expressing Concentration: (Ansel, 2010) 1. %w/w Expresses the number of grams of a constituent in 100g of solution or preparation 2. %w/v Expresses the number of grams of a constituent in 100mL of a solution or liquid preparation. 3. %v/v Expresses the number milliliters of a constituent in 100mL of solution or liquid preparation

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Prelims

2018 - 2019

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1. 2. 3. 4.

Aqueous ➢ Acidimetry ➢ Alkalimetry Non Aqueous ➢ Acidimetry ➢ Alkalimetry

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Mohr (Direct, with K 2CrO4 as indicator) Fajans (Direct) Volhard (Residual)

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Direct Indirect Residual Displacement

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Permanganometry Iodimetry / Iodometry Brominimetry Cerimetry

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Conducted by introducing a standard acid solution, gradually, from a buret into a solution of the base b eing assayed, until chemically equivalent amounts of each have reacted as shown by some change in properties of the mixture

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Used whenever the endpoint of a direct titration deviates appreciably from the stoichiometric points for some reason When the substance to be assayed does not give a distinct, sharp endpoint with an indicator by direct titration

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Reaction must proceed to completion (k = 108) Reaction must proceed in a stoichiometric manner Suitable endpoint detecting device must be available (for Direct titrimetric methods) The reaction must be rapid so as to obtain a discernible endpoint

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INDICATORS: Complex organic compounds used to (1) determine the endpoint in neutralization processes, (2) to determine [H+] in pH or (3) to indicate that a desired change in pH has been affected THEORIES ON INDICATORS: 1. Physicochemical 2. Organic 3. Colloidal

RULES ON INDICATOR USE: Use 3 gtts of indicator for titration, unless otherwise stated For SA + SB or SB + SA mo, mr or phen For WA + SB phen For WB + SA mr Never titrate WA + WB (no indicator) Appearance color > Disapp.



Prelims

DIRECT ACIDIMETRY Assay of Sodium Bicarbonate (Knevel & DiGangi, 1977) p.86 Analyte: NaHCO3 Titrant: 1N H2SO4 / 1N HCl Indicator: mo (for CO2 containing solutions) mEq: 0.08401 Titer: 84.01mg NaHCO3 USP Specification: 95 105%

2018 - 2019

]   100 %= [  

–

–

-

Methyl orange (mo) is used as indicator because phen and most other indicators are affected by the liberation of carbonic acid in the reaction, causing a change in color before the completion of reaction

RFIS: 1.

Use of methyl orange as indicator: phen indicator is affected by carbonic acid liberated in the rection. Reaction:

23 + 4 → 4 + 2 +  Formula:     100 %3 =           100 %3 =     

RESIDUAL ACIDIMETRY Assay of Zinc Oxide (Knevel & DiGangi, 1977) p.91 Analyte: ZnO Titrant: 1N H2SO4 and 1N NaOH Indicator: mo mEq: 0.04068 Titer: 40.68mg ZnO USP Specification: 99 100.5% Residual titration is carried out by dissolving the analyte in an accurately measured quantity of VS known to be in excess and titrating the excess of the latter with another standard solution. Each mL of 1N H2SO4 is equivalent to 40.68mg of ZnO RFIS: 1. Heating ZnO to increase solubility and

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– “activate” ZnO prior to assaying Reaction:  + 4 →4 +  Formula:     ]   100 %= [      Prepared by Manuzon


RESIDUAL ACIDIMETRY Assay of Milk of Magnesia (MOM) (Knevel & DiGangi, 1977) p. 94 Analyte: Milk of Magnesia Titrant: 1N H2SO4/1N NaOH Indicator: mr mEq: 0.02916 (as Mg(OH) 2) Titer: 29.16mg USP Specifications: 7 8.5% Mg(OH)2

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Reaction: Milk of Magnesia is dissolved in accurately measured excess of 1N sulfuric acid solution to ensure complete neutralization of all the magnesium hydroxide, with he formation of the soluble magnesium sulfate, as shown in (1):

 +  →4 + 2 1 -

The excess acid in (1) is then determined by residual titration with 1N NaOH, using methyl red (mr) as indicator, shown in (2):

 +2 → 4 + 2 2 Formula:

    ]   100 % = [       ]   100 %= [  

Nitrogen Determination by the Kjeldahl Method (Knevel & DiGangi, 1977) p.99 Method I Macro method Used if nitrates/nitrites are not present One (1) gram of sample is used Method II Semi micro method in which smaller samples are employed using a semi-micro Kjeldahl apparatus

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Prelims

Two to three milligrams of sample is used

   ]  100 %= [   

2018 - 2019

Assay of Aspirin USP (Knevel & DiGangi, 1977) p.111 Analyte: aspirin (ASA), C9H8O4 Titrant: 0.5N NaOH/ 0.5N H2SO4 Indicator: phen mEq: 0.04504 USP Specification: 99.5 100.5%

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Reaction: -

titrant used is base and the analyte used is acid mr and phen can be used as indicators in most inorganic acids phen mostly used in organic acids thymol blue, bromothymol blue and thymophthalein also employed as indicator for most acids

(1) neutralization of hydrolysis of ASA O

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DIRECT ALKALIMETRY

O

OH

Blank determination done without the analyte used to lessen titration error and when the analyte reacts too slowly with the titrant because of poor solubility Formula:

)     100 %= (      = ℎ

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by

OH

O

OH

+

H3C OH

(2) Neutralization of the carboxyl group of ASA O

O

OH

-

-

OH

O

+

Formula:

RESIDUAL ALKALIMETRY

acid

CH3

OH

    100 %   =    

free

O

Assay of Hydrochloric Acid (Knevel & DiGangi, 1977) p.104 Analyte: Hydrochloric Acid Titrant: 1N NaOH Indicator: mr mEq: 0.03646 USP Specification: for conc. HCl: 36.5% - 38% w/w for dil. HCl: 9.5 1- 10.5% w/v

the

Na Na

OH

+

Nonaqueous Titrimetry is used when the substance to be assayed in poorly soluble in water. Moisture content is held at less than 0.05% so as to not have any appreciable effect on the endpoint Advantages ✓ It overcomes the disadvantage of

analyte’s poor solubility and weak

reactivity with water Simplicity, speed, precision and accuracy are equivalent to those of classical procedures Disadvantages  Moisture is to be avoided, since it (H2O) would compete with the weak nitrogen bases for the HClO 4 and the sharpness of endpoint would be lost  Greater care in the control of temp during standardization ✓


H

OH


Prelims

2018 - 2019

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Titrant is acid and analyte is base

Solvents: Either relatively neutral or acidic in nature Neutral solvents: acetonitrile, alcohols, chloroform, benzene, dioxane, ethyl acetate Acidic solvents: formic acid, glacial acetic acid, propionic acids, acetic anhydride, sulfonyl chloride Sample: Weakly basic substances such as: Amines Amine Salts Heterocyclic nitrogen compounds Alkali salts of organic acids Alkali salts of weak inorganic acids Amino Acids

Solvent: Strong bases can be used as solvents for the titration of weak acids and enols Examples: Ethylenediamine n- butylamine Morpholine Weaker bases which can be used as solvents for medium strength acidic substances: Examples: Dimethylformamide Pyridine Sample: Acid anhydrides, acid halides, acids, amino acids, enols, imides, pyrroles, sulfonamides, organic salts of inorganic acids, phenols

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Titrant: HClO4 in glacial HAc , Dioxane or HBr Perchloric acid is the strongest of the commonly known acids, which gives excellent results with practically all the known weak bases Indicators: INDICATOR

Acid

Base

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Crystal violet

Violet

Quinaldine red

Colorles s

Yellow green Red Magenta

α– naphtholbenzein

Pink

Green

Malachite green

Yellow

Green

For relatively stronger bases: Methyl Red (mr) Methyl Orange (mo) Thymol Blue

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Titrant used is base and the analyte is an acid Titrant: Official bases include Sodium methoxide and Lithium methoxide

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Prelims

2018 - 2019

Table 1: Summary of information: Acidimetry and Alkalimetry (Aqueous and Nonaqueous) (Cascabel, 2017)

VS 1 std

H2SO4, HCl -

Indicator

mo, mr, phen

HClO4 KHP Crystal violet Malachite green

Caffeine, NaOH, NaHCO3, Na2CO3, Ana salicylate MOM, ZnO, NaK Tartrate

Direct Residual

Metacholine

NaOH, KOH KHP

Na/Li methoxide Benzoic acid

mo, mr, phen

Azo violet

HCl, H3PO4, H3BO3

Phenytoin

ASA

Table 2. Summary of Assays in Quality Control 1 Laboratory: Acidimetry and Alkalimetry EXPT

ASSAY

METHOD

NaHCO3

1!

ZnO

2!

MOM

2!

C4H6O6 (TA)

1@

C9H8O4 (ASA)

2@

LEGEND: 1 DIRECT 2 RESIDUAL ! ACIDIMETRY @ - ALKALIMETRY

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VS 1N HCl 1N H2SO4 1N NaOH 1N H2SO4 1N NaOH 1N NaOH 0.5N NaOH 0.5N H2SO4

INDICATOR

MW

TITER

USP LIMIT

mo

84.01g/mol

84.0100

+

mo

81.38g/mol

40.6800

~

mr

50.31g/mol

29.1600

X

phen

150.09g/mol

75.0400

*

phen

180.16g/mol

45.0400

/

– – – – – –

+ - 95 105% ~ - 99 100.5% * - 99.7 100.5% x 7.0 8.5% as Mg(OH)2 / - 99.5 100.5% Table 3. Summary of Formulas

For Standardization:

   =

 

For Blank Determination:

%= −     100 %= −     100

For Titer value computations:

  1    =   Direct Titration Method:

%=     100    100 %=     Residual Titration Method:

]    100 %= [  −    [   ]     100   −  %=    Prepared by Manuzon




Prelims

2018 - 2019

PROBLEM SOLVING Assay of Sodium Bicarbonate: 1. 2.

If exactly 3.5g of NaHCO3 is dissolved in 25mL of water, what will be the N of the solution? (MW; 84.01g) If a 0.2800g sample of sodium bicarbonate (96.5% NaHCO3) is titrated with 0.9165N sulfuric acid, what volume of the acid would be required to produce an endpoint?

Assay of Zinc Oxide 1. 2.

Calculate the titer value of 1N H2So4 for zinc oxide (MW: Zn = 65.38; O = 16) If 2.0g of ZnO were treated with 50mL of 1.123N sulfuric acid, and 27.6mL of 0.9765N NaOH were required in the back titration. Calculate the % ZnO in the sample

Assay of Milk of Magnesia 1. 2.

What is the percent magnesium hydroxide, if a sample of magnesia magma weighing 5.2430g when dissolved in 25mL of 0.9915N H2SO4 required 9.85mL of 1.1402N NaOH to titrate the excess acid? Calculate the MgO content in a 12.32g sample of Milk of magnesia, which was dissolved in 50mL of 1.0340N sulfuric acid, producing a mixture that required 24.60mL of 1.1255N NaOH

Kjeldahl Method 1.

2.

The ammonia from a 6.20g sample of an organic nitrogen compound was distilled into 50mL of 0.1248N sulfuric acid, and the mixture was titrated with 22.45mL of 0.0965N NaOH. Calculate the %N and %protein in the sample The Kjeldahl procedure was used to analyze 256mcL of a solution containing 37.9mg prot ein/mL. The liberated ammonia was collected in 5mL of 0.0336M HCl, and the remaining acid required 6.34mL of 0.010M NaOH for complete titration. What is %w/v of nitrogen in the protein? (MW = 14.01g/mol)

Assay of Hydrochloric Acid 1.

2.

A 4.0520g sample of HCl, sp. gr. 1.18, required 44.15mL of 0.9035N NaOH i n a titration. Calculate a. %w/w HCl b. HCl content c. Normality d. Titer of Na2CO3 of the sample (MW: 105.99g/mol) A 4.59mL sample of HCl, specific gravity 1.3, required 50.5mL of 0.9544N NaOH in a titration. Calculate the %w/w HCl in the sample (MW: 36.46g/mol)

Assay of Sulfuric Acid 1. A 10 mL sample of sulfuric acid solution required 16.85mL of NaOH in a titration. Each mL of the NaOH solution was equivalent to 0.2477g of potassium hydrogen phthalate. Calculate the sulfuric acid content in %w/v. (MW KHP: 204.22g/mol; MW H2SO4 = 98.09g/mol)

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Residual Titration using Blank Determination: 1. Methylparaben (MP) is used in pharmacy as a preservative in pharmaceutical preparations. From the following procedure and experimental data, calculate the percent purity of a sample of this material: Place in a flask about 2g of MP, accurately weighed, add 40mL of 1N NaOH, cover with a watch glass and boil gently for 1hr. Cool, add bromothymol blue indicator, and titrate exc ess NaOH with 1N sulfuric acid. Run a blank in the usual manner. Each milliliter of 1N NaOH consumed is equivalent to 152.2mg of methylparaben

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Prelims

Experimental Data: Weight of sample mL of 1.100N sulfuric acid used in blank titration mL of 1.100 N sulfuric acid used in sample titration

2018 - 2019

2.10g 41.00 31.00

Nonaqueous Titrimetry: 1.

A sample of chlorpheniramine maleate weighing 0.502g was assayed by nonaqueous titrimetry using 22.2mL of perchloric acid with normality of 0.1125. Calculate the % purity of the sample. Each milliliter of 0.1N perchloric acid is equivalent to 19.54mg of C 16H19ClN2*C4H4O4

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Midterms

2018 - 2019

Formula:

)    (     (  ) =   0.16907 

References:

Cascabel, K. M. (2017). Quality Control and Quality Assurance. Module 6 - Quality Assurance/Quality Control . Harris, D. C. (2010). Quantitative Chemical Analysis (8th ed.). New York, NY: W.H. Freeman and Company. Knevel, A. M., & DiGangi, F. E. (1977). Jenkins' Quantitative Pharmaceutical Chemistry. McGraw - Hill Inc.

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analyte + titrant ---> precipitate The approach assumes that under the experimental conditions used, the product is virtually insoluble. Indicators used in official volumetric assays Ferric 8g FAS to Direct and ammonium Red color 100mL Residual sulfate endpoint water titrations (FAS) Potassium 10g rgt to Red ppt of Mohr chromate 100mL silver titrations TS water chromate

Adsorption indicators

Various

DCF: Eosin Y: TEE:

Standard Solutions used in Official Assays 1. 0.1N Silver Nitrate (AgNO3) Preparation: Molecular Wt. 169.87g/mol Primary Standard NaCl

–

0.1N Ammonium thiocyanate (NH4SCN) Molecular Wt. Secondary Standard Indicator

76.14g/mol 0.1N AgNO3 FAS

Formula:

Determination of the End Point 1. Cessation of precipitation or appearance of turbidity 2. Use of internal indicators 3. Instrumental methods amperometric, potentiometric, etc. As with other types of reactions, the formation of a precipitate can be used as the basis of a titration:

Analyses of halides by direct titration with AgNO3

2.

Prepared by Manuzon Crucis, P. & Lapuz, A.M.

  =  

Fajans Method (Direct Method using Adsorption Indicator) Adsorption indicator method Endpoint reaction occurs on the surface of the AgCl precipitate Relies on the change in the primary adsorbed ion which occurs when titration goes past the equivalence point. Mohr Method (Direct Method using K 2CrO4) Potassium chromate forms a red ppt seen against a bg of white AgCl Relies on the Ksp differences of silver chloride and silver chromate Volhard Method (Residual Titration Method) Method is based on the complete precipitation of insoluble silver salts from HNO3 soln by addition of xcs AgNO3 to a soluble salt and determination of amount of silver nitrate solution by xcs residual titration with standard NH4SCN solution. Ferric ammonium sulfate is indicator Steps: ➢ Excess Ag+ is added to the sample ➢ AgCl is removed via filtration ➢ Excess Ag+ is titrated with SCN ➢ Fe3+ acts as an indicator forming a complex with SCN-, after all Ag ions has been consumed. Assay of NaCl (Knevel & DiGangi, 1977) Official Requirement is 99 100.5% Use either Fajans/Volhard Indicator is FAS (ferric alum) (Volhard) Indicator is Eosin Y (Fajans)

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Midterms

2018 - 2019

RFIS: 1. HNO3 prevent precipitation of silver as carbonate, phosphate, etc. as well as prevents hydrolysis of the ferric alum

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Calmagite wine red Murexide (yellow Co, Ni, Cu; red Ca) Xylenol orange red Pyrocatechol violet - blue Qualities of the indicator: Sharpness of color change Specificity of indicator for the metal ion Stability constant smaller than that on the metal EDTA complex •

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•

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• •

Pertinent Chemical Reactions: 1. Reaction of AgCl to NH4SCN

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•

  ⇌↓  

•

Formula:

 ] 0.05844  100 % [      )  = (      (  )  =    

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Complex resulting compound formed when a metal ion combines with a molecule which can donate electrons

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Chelate resulting complex formed if the combining molecule contains two or more groups that can donate electrons

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Ligand A molecule which provides groups for attachment to metal ions -

In add EDTA complexation reactions, the ratio of the EDTA to the metal ion is 1:1 The four oxygen and two nitrogen atoms of the EDTA molecule capable of entering a complexation reaction with a metal ion makes it a hexadentate molecule For successful titrations with EDTA. The stability constants of the complex formed must be greater than 8. Indicators in EDTA Titrations: The most common way to detect end point in EDTA titrations is with a metal ion indicator. Metal ion indicators are compounds which change color when they bind to a metal ion (Harris, 2010) Metal Ion Indicators: Azo dyes, phthaleins, triphenylmethane dyes, xylenol orange, hydrocathechol violet, Eriochrome back T Color of the metal ion complex:

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•

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Direct Titration Methods in Complexometry Usual metal ions determined via direct titration w/ EDTA include Ca2+, Mg2+ and Zn2+ Preparation of 0.05M Disodium EDTA Primary Std. CaCO3 MW 100.09 g/moL mEq 0.050045 Indicator

Hydroxynaphthol blue

Endpoint

Blue

Formula for Molarity of Disodium EDTA:

RFIS: 1.

2.

    = ℎ 100.09    –  2 →   NaOH – alkalinizes the solution to a pH of HCl solubilizes CaCO3 by converting it to CaCl2

about 13 so that the Ca-EDTA complex would be stable and any Mg present would not contaminate EDTA Titration Techniques Direct Residual Displacement Indirect Masking and Masking Agents (Knevel & DiGangi, 1977) Masking is a term used to indicate the determination of a metal in the presence o f another metal Accomplished by adjusting the pH of the titration medium



Midterms

Examples: Bi (Bismuth) complexes at pH = 2 Ca titration is done at pH = 13 (see above method) Use of auxiliary complexing agents, an agent used to permit many metals to be titrated in alkaline solutions with EDTA (Harris, 2010). This reagent is a ligand such as ammonia, tartrate, citrate, or triethanolamine that binds the metal strongly enough to prevent metal hydroxide precipitation, but weak enough to give up the metal ion when EDTA is added. Triethanolamine suppresses Al-EDTA in Mg-EDTA titration Thioglycol inactivates metals like Hg and Cu to allow titration of Zn at pH = 6 KCN inactivates Co, Ni, Cu and Zn AlF3 masks Mg and Al to allow Zn titration Demasking Agents Releases the metal ion from the masking agent Example: Formaldehyde • •

•

•

•

• •

Residual Titration Methods in Complexometry Applies to the analysis of aluminum and bismuth compounds Bi forms a highly stable complex and can be titrated at a pH as low as 1 or 2

NB: VILEORA and VDGEROA OXIDATION REDUCTION Valence Increase Decrease Electrons Loss Gain Agent RA OA Formula for mEq of OA and RA:

   =       =   

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2018 - 2019 Table of Oxidizing Agents and their mEq Factor Std. Solution Formula f x 1000 Potassium KMnO4 5000 permanganate Potassium K2Cr2O7 6000 dichromate Potassium ferricyanide Potassium KBrO3 6000 bromate Ceric sulfate Ce(SO4)2 1000 Iodine I2 2000 Bromine Br2 2000 Ferric alum FeNH4(SO4)2 Table of Reducing Agents and their mEq Factor Std. Solution Formula f x 1000 Ferrous Fe(NH4)2(SO4)2 ammonium 1000 6H2O sulfate Potassium KAsO2 2000 arsenite Titanium TiCl3 1000 chloride Sodium Na2S2O3 1000 thiosulfate Arsenic As2O3 4000 trioxide Oxalic acid H2C2O4 2000

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KMnO4 is a self-indicator Endpoint is a distinct pink color Titration with KMnO4 should never be titrated from Mohr burets Na2C2O4 is the best standard to use for KMnO4 standardization Sulfuric acid is added to prevent formation of MnO2

Assay of H2O2 (Knevel & DiGangi, 1977) Expressed in %w/v Should contain 2.5 3.5g/100mL (10 volumes) or 5.0 7.0g/100mL (20 volumes) H2O2 is an oxidizing agent but acts as a reducing agent in this assay

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Midterms

Assay of Cherry Juice for Malic Acid (Knevel & DiGangi, 1977) -

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Indirect method of MnO4- oxidation Malic acid is converted to an equivalent amt of calcium salt, then converted to CaC2O4, with the oxalate being liberated and oxidized with permanganate Titer value: 6.704mg of malic acid

2018 - 2019

Assay of Ascorbic Acid A solution of dichlorophenol indophenol is standardized using ascorbic acid (RS), USP. Dichlorophenol indophenol is used as a standard OA in the determination of ascorbic acid in ascorbic acid tablets and injections. No indicator is necessary Blue in alkali Red in acid Colorless in reduced form Titration is done in the presence of metaphosphoric acid and acetic acid with the standard solution, until a distinct rose

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–

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Assay of NaNO2 (Knevel & DiGangi, 1977) RFIS: Since NaNO2 is deliquescent, weigh in a -

-

stoppered bottle NaNO 2 is introduced beneath the surface :

this is because nitrous acid (HNO2) is oxidized by KMnO4 to HNO3, and if HNO2 is acidified by H2SO4, HNO2 is easily volatilized therefore it must be introduced beneath the KMnO4 to prevent loss. Allowing to stand for 5 min : ensures oxidation completion Heating to 40 degrees Celsius: optimal temperature for reaction completion

Formula:

%   100      2000 =   

• •

– pink color persisting for at least 5s Analyte Method VS Indicator Endpoint

IO METRY Reducing Agent rect 0.1N Iodine VS Starch TS Before titration Blue black

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I DOMETRY xidizing Agent Residual 0.1N Na2S2O3 Starch TS Before EP Colorless

Preparation of Starch TS (indicator) Notes: 1. Should be freshly prepared deteriorates rapidly 2. In hot water, starch granules burst and form a colloidal dispersion: Beta amylose - aka soluble starch Alpha amylose - aka amylopectin, insoluble starch 3. Mercuric iodide (HgCl 2) is used as a preservative for Starch TS

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Ce(SO4)2 in dil. H2SO4 is a strong OA Considerably more stable than KMnO4 Indicator is orthophenanthroline

  ++ → −+ ⇌    -

-

-

(above reaction) from orthophenanthroline (colorless) to ferrous complex (red) to ferric complex (blue) Arsenic trioxide (As2O3) is the primary standard Osmium tetroxide added as catalyst for the reaction between Ce4+ and the arsenite ion (AsO2-) Example of assay using cerimetry: Assay of FeSO4 tablets

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Preparation of 0.1N Iodine Solution Primary Standard: Arsenic Trioxide Solubilizing Agent: Potassium Iodide Indicator: Starch TS Buffering Agent: NaHCO3 Secondary Indicator: Methyl Orange (for neutralizing the excess NaOH with HCl) • • • • •

    =   0.04946

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Midterms

2018 - 2019 Formula:

Preparation of 0.1N Sodium Thiosulfate Primary Standard: K2Cr2O7 Oxidizes iodide ion in presence of acid to an equivalent amt of iodine Prepared using CO2 free water Uses Na2CO3 as preservative to prevent hydrolysis CHCl3 (trichloromethane, chloroform) is added to prevent bacterial growth.

8.806  100 %  =  

• •

–

• •

•

Chemical Reaction Involved:

 614 → 3 2 8 7 Preparation of 0.1N Potassium Arsenite Primary Standard: Arsenic trioxide KOH neutralizes arsenic trioxide and forms potassium arsenite (KAsO2) KHCO3 alkalinizes (to about pH =9) which is necessary for accurate results and a rapid reaction with iodine. • •

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•

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Liberation of Iodine from KI and Titration with Na2S2O3 Used for substances that are OA which cannot be determined via direct titration with a std solution of an RA are assayed indirectly

Examples: Assay of Selenium Sulfide Assay of NaOCl Assay of CuSO4 • • •

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Assay of NaOCl USP Spec: 4-6% w/w Reagents: KI, HAc VS: 0.1N Na2S2O3 Indicator: Starch TS

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Bromine is employed as an OA in place of iodine for the analysis of aniline, phenol and resorcinol Formation of a water insoluble brominated product such as tribromoaniline and tribromophenol

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Preparation of 0.1N Bromine VS aka Koppeschaar’s Solution No primary standard Secondary Standard: Na2S2O3 Reactions:

56  →6 3  3 2  →  2  2 2  Assay of Phenol USP Spec: 99 100.5% Reagents: HCl, KI, CHCl 3 VS: 0.1N Br2 and 0.1N Na2S2O3 Indicator: Starch TS Titer: 1.569mg

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Reactions:

5 6 →6 3  3 3   → 3 2  →  2  22 

Formula:

    1.569  100 %ℎ =     

Reaction:

2 →       2 2 

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Assay of Ascorbic Acid USP Spec: 99 100.5% VS: 0.1N I2 Indicator: Starch TS Titer: 8.806 mg Strong RA, wherein titration with iodine oxidizes it to dehydroascorbic acid and iodine is reduced to iodide ion.

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KIO3 may be used as the OA in the assay of many substances such as iodides, arsenite and other RAs



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Midterms

2018 - 2019

The assay of sulfa drugs and other cmpds containing an aryl amino group by diazotization with NaNO2 are not strictly iodometric methods

Preparation of 0.1M Sodium Nitrite (NaNO2) -

Primary Standard: Sulfanilamide RS

RFIS: EP is det by liberation of I2 from iodide Reaction kept cold: will decompose forming phenol products capable of reacting further with HNO3

• •

•

Drying at 105 deg Celsius

•

Indicator: Starch iodide paper

Reactions:

 2 →       → +  2 − 2 2  2 →  2 2 Assay of Sulfathiazole (reaction below): O

O

N

O

O

N

S

S NH

NH

S

S

O

+ H

-

+

N

-

+

+ Cl

HCl

O

+

H

OH

+

N

H2N N

VS: 0.1M NaNO2 Indicator: Starch Iodide Paper Titer: 25.53mg

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Midterms

2018 - 2019

Table 1. Summary of Information: Precipitimetry and Complexometry (Cascabel, 2017) VOLUMETRIC PRECIPITIMETRY Method Manifestation VS Indicators 1 Std Example/s Volhard NaCl Colored ppt. 0.1N NH4SCN Ferric alum Silver nitrate (resid.) Aminophylline nd Mohr 2 ppt. 0.1N AgNO3 K2CrO4 NaCl SLS DCF Change in color Phenylephrine Fajans Eosin Y NaCl of ppt Tubocurarine TEE

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Table 2. Summary of Information: Reduction Oxidation Methods (Cascabel, 2017) Permanganometry Cerimetry Iodimetry (Direct) Iodometry Brominimetry 0.1N Na2S2O3 0.1N KMnO4 Ce(SO4)2 0.1N Iodine 0.1N Br2 KAsO2

VS 1 Std Indicator Direct

KMnO4

Ferroin Menadione

TiO2

Starch TS Oxidizing Agts

Na metabisulfite Na thioglycolate Iodine tincture RA + I2 -> Iodide

Residual Endpoint •

Starch TS

Reducing Agts

Cherry Juice (Malic acid)

Indirect

Starch TS

Ferric/cupric salt Resorcinol OA + xcs KI -> Iodine

NaNO2 and KNO2 Purple R -> B Blue Colorless Diazotization Assay (direct titration with NaNO2 sulfa containing drugs)

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Table 3. Summary of Assays in Quality Control 1 Laboratory: Precipitimetry, Complexometry, and Redox Tirations EXPT

ASSAY

METHOD

VS

NaCl

1P

NH4Cl

2P

CaSO4

1C

H2O2

1[#]

NaNO2

2[#]

NaClO

1[$]

0.1N Na2S2O3

C6H8O6 (ascorbic)

1[%]

C6H5OH (phenol)

2[$]

0.1N I2 0.1N Br2 0.1N Na2S2O3

C9H9N3O2S2 (sulfathiazole

1[$]

–

0.1N AgNO3 0.1N AgNO3 0.1N NH4SCN 0.05M EDTA 0.1N KMnO4 0.1N H2C2O4 0.1N KMnO4

0.1M NaNO2


INDICATOR

MW

TITER

USP LIMIT

Eosin Y

58.44g/mol

5.8440

~

Ferric alum

53.50g/mol

5.3490

~

Hnb

136.15g/mol

6.8071

=

KMnO4

34.04g/mol

1.7010

^

KMnO4

69.00g/mol

3.4500

>

Starch (BEP) Starch (B)

74.44g/mol

3.7220

<

176.14g/mol

8.8060

~

Starch (B)

94.11g/mol

1.5690

~

Starch (SP)

255.31g/mol

25.5300

~


Quality Control 1 w/ D.T.A. LEGEND: 1 DIRECT 2 RESIDUAL P PRECIPITIMETY C COMPLEXOMETY [ ] REDOX # - Permanganometry $ - Iodometry % - Iodimetry

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Midterms

– – – –

hnb hydroxynaphthol blue B before titration BEP before endpoint SP starch iodide paper

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2018 - 2019

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~ - 99.5 100.5% = - 98 101% > - 97 101% < - 4.0 6.0% w/w ^ - 2.5 3.5g/100mL

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Midterms

2018 - 2019

PROBLEM SOLVING;

1. 2.

1. 2.

1. 2. 3.

4.

1. 2. 3.

4. 5.

6.

A 0.2285g of NaCl was assayed by the Volhard method, using 50mL of 0.0955N AgNO3 and 11.85mL of 0.1355N NH4SCN. Calculate the %NaCl What must be the N of a solution of AgNO3, so that each mL shall be equivalent to 6mg of NaCl?

How many grams of disodium EDTA is required to prepare 250mL of a 0.025M solution? What would be the titer of this solution in terms of a) CaCl2 with 2H2O, b) MgSO 4 and c) ZnCl2? A 200-milligram sample of pure CaCO 3 was acidified and dissolved in 500mL of solution. A 50mL sample required 25mL of an EDTA solution to titration. Find the molarity of the EDTA solution

A 0.2295g sample of Na2C2O4 (97.8% pure) required 35.12mL of a KMnO 4 solution in a titration. What is the normality of the permanganate solution? What volume of a 0.1225N NaOH solution would be re quired in a titration of a 0.1065 sample of oxalic acid, if a 0.1126g sample of oxalic acid required 24.65mL of 0.0965N KMnO4 in a titration? A 2.00mL sample of hydrogen peroxide solution required 8.5mL of a permanganate solution in titration. If each mL of the permanganate solution is equivalent to 0.007295g of Fe, what %w/v of H2O2 was in the sample? A 1.100g sample of sodium nitrite was dissolved in enough water to make 100mL. A 1 0mL sample was added to 50mL of 0.1N KMnO4 in the presence of sulfuric acid. The mixture was treated with 25mL of 0.0975N oxalic acid and titrated with 4.58mL of KMnO4. Calculate the %NaNO2 in the sample

What is the normality of a solution containing 0.0136g of iodine, per milliliter? What weight of arsenic trioxide (98.73%) would be used as a sample, so that 35.00mL of 0.1N iodine would be needed to titrate it? A 4.0050g sample of chlorinated lime was mixed with enough water to make 1000mL. A 100mL sample of the mixture was treated with KI and HAc, then titrated with 22.61mL of sodium thiosulfate. A 20mL sample was found to be equivalent to 0.3689g of pure iodine. Calculate the available chlorine content of the chlorinated lime What volume of 0.1056N sodium thiosulfate would be required in the titration of the iodine, equivalent to 0.2g of CuSO4? How much KBrO3 must be present in a solution which when treated with KBr and HCl, will liberate bromine equivalent to 45mL of 0.0915N Na2S2O3? If the volume of KBrO3 were 35mL, what will be its normality? A 1.45g sample of liquefied phenol was dissolved in enough water to make 1L. Thirty milliliters of the sample solution was treated with bromine solution and HCl. The mixture was then treated with KI and was titrated with 7.38mL of 0.1N Na2S2O3. It was also found out that 21mL of 0.1N Na2S2O3 was required in the titration of the iodine liberated when 20mL of the bromine solution was treated with KI and HCl. Calculate the phenol content in the original sample

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Midterms

2018 - 2019

Additional Problems 1.

2.

The amount of iron in a meteorite is determined by a redox titration using KMnO4 as the titrant. A 0.4185g sample is dissolved in acid and liberated Fe3+ quantitatively reduced to Fe2+ using a Walden redactor. Titrating with 0.025M KMnO4 requires 41.27mL to reach the endpoint. Determine the % w/w Fe2O3 in the sample of meteorite. Under basic conditions, permanganate is used as a titrant for the analysis of Mn2+, with both the analyte and the titrant forming MnO2. In the analysis of a mineral sample for manganese, a 0.5165g sample is dissolved and the manganese reduced to Mn2+. The solution is made basic and titrated with 0.03358M KMnO4, requiring 34.88mL to reach the endpoint. Calculate the %w/w Mn in the mineral sample.

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