PHARMACEUTICAL ANALYTICAL CHEMISTRY

1 PHARMACEUTICAL ANALYTICAL CHEMISTRY 0510113 Dr. Ahmad Najjar Faculty of Pharmacy Department of Pharmaceutical Sciences First Semester, 2017/2018

2 CHAPTER 1 ANALYTICAL OBJECTIVES

3 ANALYTICAL CHEMISTRY / PHARMACEUTICAL ANALYSIS Analytical chemistry is the study of the separation, identification, and quantification of the chemical components of natural and artificial materials. Analytical science deals with the chemical characterization of matter what, how much? Pharmaceutical analysis is the application of the knowledge of analytical chemistry to analyze pharmaceutical raw materials or finished products where the principle of analytical chemistry is applied

4 Qualitative and Quantitative Analysis The analyst must know what information is really needed, and obtain a representative sample.

5 ANALYTICAL CHEMISTRY 1- Qualitative Analytical chemistry: - Focuses on the presence or absence of analyte - Identification of analyte - Recognized by color, boiling point, solubility, taste, etc. 2- Quantitative Analytical Chemistry: - Determination of concentration - Gravimetric or titrimetric measurements, or instrumental methods used are depending on physical properties measurements like conductivity, electrode potential, light emission absorption, mass to charge ratio, fluorescence, and many more

6 Quantitative Analytical methods Quantitative Analytical methods are classified according to the final measurement step into: Volumetric methods (volume) Gravimetric methods (weight) Instrumental methods (absorbance, optical rotation, etc ) Few measurements are specific, so operations are performed to achieve high selectivity. You must select the appropriate method for measurement.

7 instrumental QUANTITATIVE ANALYTICAL METHODS

8 THE ANALYTICAL PROCESS

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13 LABORATORY TOOLS Volume measuring Read from meniscus at eye level

14 LABORATORY TOOLS Filtration

15 LABORATORY TOOLS Temperature measurements

16 LABORATORY TOOLS Weighing Analytical balance Top loading balance Triple beam balance Spatula Weighing boats

17 CHAPTER 5 STOICHIOMETRIC CALCULATIONS Learning Objectives How to calculate molarities and moles How to express analytical results How to calculate weight and percent analyted from molarities, volumes, and reaction ratios Weight relationships for gravimetric analysis

18 Revision of basic concepts

19 Review of elementary concepts and mathematical calculations Main laboratory techniques: weighing, volume measurements, drying, solutions preparation, decantation

20 SI measuring units

21 MOLAR MASS It is the mass of one mole of substance, it is called: Molar mass, M.wt. or f.wt., its unit is (g/mol) or (mg/mmol) Molar mass is calculated from the atomic masses of individual atoms composing the molecule. KMnO 4? NaOH? CH 3 COOH?

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23 MOLE 1 Mole of molecules avogadro s num. of molecules ( avogadro s num. = 6.02x10 23 )

24 MOLE also moles of substance = mass of substance / M.wt e.g. 36 g of H 2 O contains 36 g 18 g/mol 2 molh O 2

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26 Example (a) How many glucose molecules are in 5.23 g of C 6 H 12 O 6? (molar mass is 180.0 g/mol) (b) How many oxygen atoms are in this sample? Answer (a) Firstly, calculate the number of moles then calculate the number of molecules from the number of moles mass 5.23 moles 0.0291 mol molar mass 180 number of molecules number of moles Avogadro' s no. 0.0291 6.022x10 23 1.75 10 22 (b) Each molecule of glucose has 6 atoms of oxygen, therefore number of oxygen atoms 6 number of glucose moelcules 6 1.75 10 22 1.05 10 23

27 MOLE AND RATIO OF ATOMS IN THE MOLECULE e.g. Glucose C 6 H 12 O 6 the atomic ratios between C:H:O is 6:12:6 Q. 3 moles of Fe 2 O 3 contains? mole of Fe atoms and? mole of O atoms.

28 MOLE AND STOICHIOMETRY Stoichiometry is the ratio between substances in the balance chemical equation e.g. Ca(OH) 2 Ca 2+ + 2OH -, the ratio between Ca(OH) 2 :Ca 2+ :OH - is 1:1:2 Q. If we have 5 moles of Ca(OH) 2, how many moles of OH will produce? Q. If you have this equation, so how many sandwich could you make by 10 slices of bread and 10 slices of cheese?

29 Moles of A mass of A (this is Molar mass of A used generally if A is solid substance) Moles of A Molar concentration of A Volume of solution (this is used generally if A is solutesubstancein a solution) Pressure Volume Moles of A (this is used generally if R(constant) Temperature A is gaseous substance) Moles of A Number of A particles (this is Avogadro' s Number (constant) used generally if number of A is known)

30 CONCENTRATION Concentration is The amount of a substance per defined space We refer to the chemical species that we are looking for its concentration by Analyte, Constituent, Substance, or Solute while the space is called Sample, Solution, Mixture, Matrix, Medium or Solvent The most known concentration unit in stoichiometric calculations is the molar concentration c and it is usually called molarity M. Molarity (M) unit [used for solutions and it measure moles of solute per liters of solution] Molarity = moles of substance / volume of solution (L) M = mol / v Q. Calculate the molarity of Cl - in a solution made by dissolving 20 g of BaCl 2 in 360 ml water? (M.wt of BaCl 2 is 208 g/mol)

31 CONCENTRATION Solution Preparation steps

32 (M.wt. AgNO 3 is 169.9 g/mol) (M.wt. Na 2 SO 4 is 142 g/mol)

33 CONCENTRATION UNITS For solutions also we can use the unit of g/ml or g/l or mg/l to express the mass of solute per volume of solution (mass concentration p ) concentrat ion (g/l) mass of volume of solute(g) solution (L) or M M.wt (At.wt. K is 39.1 g/mol)

34 CONCENTRATION UNITS (M.wt. NaCl is 58.4 g/mol) Normality (N) unit Although molarity is widely used in chemistry, some chemists use a unit of concentration in quantitative analysis called normality (N). A one-normal solution contains one equivalent per liter. An equivalent represents the mass of material providing Avogadro s number of reacting units. A reacting unit is a proton or an electron. The number of equivalents is given by the number of moles multiplied by the number of reacting units per molecule or atom; the equivalent weight is the formula weight divided by the number of reacting units (n).

35 CONCENTRATION UNITS Normality (N) No.of equivalents (eq) n Molarity Volume of solution (L) mass (g) No.of equivalents (eq) equivalent weight (g/eq) n moles M olecular weight (g/mol) equivalent weight (g/eq) n (eq/mol) Reacting units (n), For acids and bases, the number of reacting units is based on the number of protons (i.e., hydrogen ions) an acid will give or a base will react with. For oxidation reduction reactions it is based on the number of electrons an oxidizing or reducing agent will take on or supply. For most of ionic reactions it is based on the charge of the cation or anion.

36 CONCENTRATION UNITS Molality (m ) unit A one-molal solution contains one mole per 1000 g of solvent. Molality (m) No.of moles (mol) Massof Solvent (kg) The molal concentration is convenient in physicochemical measurements of the colligative properties of substances, such as freezing point depression, vapor pressure lowering, and osmotic pressure because colligative properties depend solely on the number of solute particles present in solution per mole of solvent. Molal concentrations are not temperature dependent as molar and normal concentrations. Density (D) is the mass (g) of one unit of the solution (generally ml or L)

37 Dilution Dilution is a process in which we decrease the concentration of a substance from high concentration (initial) to lower concentration (final) by adding more solvent. Number of moles is not changed, only the concentration and volume are changed, therefore Moles initial = Moles final (Conc. x Vol) i = (Conc. x Vol) f Example What will be the volume of 0.2M NaCl solution that should be taken to prepare 5L of 0.004M NaCl solution? Answer Initial: Conc. = 0.2M, Vol.=?? Final: Conc. = 0.004M, Vol.=5L (M.V) i =(MV) f 0.2xV i = 0.004x5 V i = (0.004x5)/0.2 = 0.1 L

38 Dilution Dilution steps

39 Dilution

40 Dilution

41 Concentration units Percentage unit ( % ) Percentage unit is a concentration unit generally used for solid media. It could be expressed as % % % w/w w/v v/v mass of solute(g) 100 mass of sample(g) mass of solute(g) 100 volume of sample(ml) volume of solute(ml) 100 volume of sample (ml) Q. What is the percentage concentration (% w/w ) of NaCl in a solution made by dissolving 20.0 g NaCl in 200 ml water? Q. Calculate the Na % w/w in the above solution? (M.wt. NaCl is 58.5 g/mol and At.wt. for Na is 23 g/mol) Q. What is the molar concentration (M) of Glucose solution that has %w/w of 15%? (M.wt. for glucose is 180 g/mol)

42 Concentration units Example Calculate the molarity of concentrated HCl solution that have a density of 1.188 g/ml and have % concentration of 36% w/w? (M.wt. HCl = 36.5 g/mol) Answer Molarity of mass 1L of the solution has a mass of 1188 g, Density volume mass Density volume mass 1.188g/mL 1000 ml 1188 g this this So 1L mass mass of of of the HCl solution HCl concentrated solution has contains 36% no. contains mole of HCl volume of solution (L) of of 36 HCl, so mass of HCl 1188 427.68 g HCl 100 mass HCl 427.68 g moles equal to 11.72 mol HCl M.wt.HCl 36.5 g/mol 11.72 mol HCl, then M HCl mol HCl volume of solution (L) 11.72 1 11.72M in another words, M HCl 1000 D % M.wt. w/w 1000 1.188 36 36.5 11.72 M

43 Dilution (M.wt. H 2 SO 4 is 98.1 g/mol)

44 Concentration units Part Per Million (ppm) and Part Per Billion (ppb) Units These units could be used either if the solute was present in solid, liquid or gas medium %o = [mass of substance (g) / mass of solution (g)] x 10 3 ppm = [mass of substance (g) / mass of solution (g)] x 10 6 ppb = [mass of substance (g) / mass of solution (g)] x 10 9 ppt = [mass of substance (g) / mass of solution (g)] x 10 12 - we can convert molarity to ppm if we knew the density of the solution.

45 Concentration units Final thing, reporting concentrations as different chemical species We may express results in any form of the analyte. This is often done to facilitate the interpretation by other professionals. Water hardness due to calcium ion is expressed as ppm CaCO 3.

46 Concentration units

47 HOW DO WE MAKE STOICHIOMETRIC CALCULATIONS? Chemical analysis is mainly employ the use of a balanced chemical reaction. In Volumetric or titrimetric analyses, the test substance Analyte (the substance that we need to determine its concentration) reacts with an added reagent of known concentration (standard solution). This standard solution is typically delivered from a buret, therefore it is called Titrant. Analyte concentration could be calculated from the chemical relation between these two reactants. In Gravimetric analyses, the Analyte is converted to a precipitated Product according to a balanced chemical reaction. Analyte concentration could be calculated from the chemical relation between the analyte reactant and the precipitated product.

48 HOW DO WE MAKE STOICHIOMETRIC CALCULATIONS? Titration The requirements of a titration are as follows: 1. The reaction must be stoichiometric. That is, there must be a welldefined and known reaction between the analyte and the titrant. 2. The reaction should be rapid and quantitative. That is, the equilibrium of the reaction should be far to the right so that a sufficiently sharp change will occur at the end point to obtain the desired accuracy. 3. There should be no side reactions; the reaction should be specific. 4. There should be a marked change in some property of the solution when the reaction is complete. An indicator is generally added to monitor this change. 5. The point at which an equivalent or stoichiometric amount of titrant is added is called the equivalence point. The point at which the reaction is observed to be complete is called the end point, that is, when a change in some property of the solution is detected.

49 HOW DO WE MAKE STOICHIOMETRIC CALCULATIONS? Standard Solutions A standard solution is prepared by dissolving an accurately weighed quantity of a highly pure material called a primary standard and diluting to an accurately known volume in a volumetric flask. Alternatively, if the material is not sufficiently pure, a solution is prepared to give approximately the desired concentration, and this is standardized by titrating a weighed quantity of a primary standard. A solution standardized by titrating a primary standard is itself a secondary standard. A primary standard should fulfill these requirements: 1. It should be highly pure, with accurately known impurity. 2. It should be stable to drying temperatures, and indefinitely at room temperature. 3. It should be readily and relatively inexpensively available. 4. Although not essential, it should have a high formula weight. 5. If it is to be used in titration, it should possess the properties required for a titration listed above. In particular, the equilibrium of the reaction should be far to the right so that a sharp end point will be obtained.

50 HOW DO WE MAKE STOICHIOMETRIC CALCULATIONS? Classification of Titration Methods 1. Acid Base. The end points of these titrations are easy to detect, either by means of an indicator or by following the change in ph with a ph meter. 2. Precipitation. Titrant forms an insoluble product with the analyte. Again, indicators can be used to detect the end point, or the potential of the solution can be monitored electrically. 3. Complexometric. Titrant is a reagent that forms a water-soluble complex with the analyte, a metal ion. The titrant is often a chelating agent like Ethylenediaminetetraacetic acid (EDTA). Indicators can be used to form a highly colored complex with the metal ion. 4. Reduction Oxidation. These redox titrations involve the titration of an oxidizing agent with a reducing agent, or vice versa. Appropriate indicators for these titrations are available; various electrometric means to detect the end point may also be used.

51 VOLUMETRIC CALCULATIONS

52 VOLUMETRIC CALCULATIONS

53 VOLUMETRIC CALCULATIONS

54 VOLUMETRIC CALCULATIONS

55 VOLUMETRIC CALCULATIONS

56 GRAVIMETRIC CALCULATIONS

57 CHAPTER 6 CHEMICAL EQUILIBRIUM Learning Objectives The equilibrium constant Calculation of equilibrium concentrations The systematic approach to equilibrium calculations: mass balance and charge balance equations Activity and activity coefficients

58 Review of Equilibrium

59 Review of Equilibrium The concentration of a pure solid or liquid is unity.

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61 Equilibrium Constants for Dissociating or Combining Species Weak Electrolytes and Precipitates When a substance dissolves in water, it will often partially or completely dissociate or ionize. Electrolytes that tend to dissociate only partially are called weak electrolytes, and those that tend to dissociate completely are strong electrolytes. Some species dissociate stepwise, and an equilibrium constant can be written for each dissociation step. A compound A 2 B, for example, may dissociate as follows:

62 Equilibrium Constants for Dissociating or Combining Species Weak Electrolytes and Precipitates When chemical species dissociate in a stepwise manner like this, the successive equilibrium constants generally become progressively smaller. For a diprotic acid (e.g., ), the dissociation of the second proton is inhibited relative to the first (K 2 < K 1 ), because the negative charge on the mono-anion makes it more difficult for the second proton to ionize. If a reaction (like AB A + B) is written in the reverse, the same equilibria apply, but the equilibrium constant is inverted. Thus, in the above example, for A + B AB, K eq(reverse) = [AB]/([A][B]) = 1/K eq(forward). If K eq for the forward reaction is 10 5, K forward = 1/K backward then K eq for the reverse reaction is 10 5.

63 Calculations Using Equilibrium Constants ** Repeat the calculations for K = 1x10-4 with and without approximation.

64 Calculations Using Equilibrium Constants The Common Ion Effect

65 Calculations Using Equilibrium Constants Equilibrium for complex systems Mass balance equations

66 Calculations Using Equilibrium Constants Equilibrium for complex systems Charge balance equations

67 Calculations Using Equilibrium Constants Equilibrium for complex systems Systematic Approach

68 Calculations Using Equilibrium Constants Equilibrium for complex systems Systematic Approach

69 Calculations Using Equilibrium Constants Equilibrium for complex systems Systematic Approach

70 Activity and Activity Coefficients The effective concentration of an ion is decreased by shielding it with other inert ions, and it represents the activity of the ion. This effective concentration of an ion in the presence of an electrolyte is called the activity of the ion. The activity of an ion a i is defined by: a i = C i f i, where C i is the concentration of the ion i and f i is its activity coefficient. The activity coefficient varies with the total number of ions in the solution and with their charge, and it is a correction for interionic attraction. In dilute solution, less than 10 4 M, the activity coefficient of a simple electrolyte is near unity, and activity is approximately equal to the concentration. Activity coefficient is a function of the total electrolyte concentration of the solution. The ionic strength is a measure of total electrolyte concentration and is defined by:

71 Activity and Activity Coefficients Debye and Huckel derived a theoretical expression for calculating activity coefficients, known as the Extended Debye Huckel equation: A and B are constants; the values are, respectively, 0.51 and 0.33 for water at 25 C. a i is the ion size parameter, which is the effective diameter of the hydrated ion in angstrom units, Å.

72 Thermodynamic Equilibrium Constant Equilibrium constants should more exactly be expressed in terms of activities rather than concentrations The numerical value of K eq holds for all activities. K eq = K eq at zero ionic strength, but at appreciable ionic strengths, a value for K eq must be calculated for each ionic strength.