MODULE 6: QUALI & QUANTI

• Qualitative Analysis


  Reveals the identity of the sample elements and compounds in a sample. Presence or absence of a component. E.g., USP ID Tests
• Quantitative Analysis


  Indicates the amount of each substance in the sample. Exact amount or proportion of component (expressed in 1% purity and compared to official compendia). E.g., Gravimetric, Volumetric, Physicochemical and Special methods of analysis
• Types of analysis based on amount of sample

  • Ultra-micro: < 1.0 mg
  • Micro: 1.0 to 10 mg
  • Semimicro/ Meso: 10 to 100 mg
  • Macro: 100 to 1000 mg
• Constituent types by analyte level

  • Major: 1 to 100%
  • Minor: 0.01 (100ppm) to 1%
  • Trace: 11 ppb to 100 ppm
  • Ultratrace: < 1 ppb
• Proximate Assay (for crude drugs)


  Total of class of plant principles (group of compounds). E.g., Total alkaloidal content in coffee beans
• Ultimate Assay (for crude drugs)


  Single chemical species (specific component). E.g., total caffeine content in coffee beans
• Proximate and Complete analysis (for chemical drugs)


  • Proximate: Partial - selected or trace compounds
  • Complete: Each constituent
• Types of analysis based on nature


  • Chemical/ General Methods: titration, gravimetry
  • Instrumental Methods: UV-Vis, IR, MS, Chromatography
  • Special Methods: for natural products; Ash content, Water content, constants for fats and fixed oils
• Types of analysis based on material


  • Chemical: chemical reagents
  • Physical: Boiling Point, Melting Point, optical purity, Refractive Index
  • Biological: potency or effectiveness of drugs: Animal models (e.g., chicken - oxytocin, Sheep - heparin); Microbial Assay - antibiotics
• Random (Intermediate) Errors


  Due to uncontrollable variables. Variations in a series of observations (by the same observer under identical conditions). Affect measure precision.
• Systematic (Determinate) Errors


  With definite value and identifiable cause. Same magnitude or replicate measurements made the same way. It can lead to bias and can affect accuracy of results. Sources: Instrumental Errors, Method Errors, Personal Errors
• Gross Errors


  Occur only occasionally, are often large, and may cause a result to be either high or low (can lead to outliers). Often the product of human errors.
• Accuracy


  Closeness of an actual value to the theoretical (true) value and is expressed by error. Measures agreement between the result and the accepted value.
• Precision


  Closeness of 2 or more actual measurements obtained in exactly the same way. Describes the reproducibility of measurements. Reported as: average deviation, standard deviation, coefficient of variation or range.
• Titrimetric (Volumetric) Analysis


  Method in which the volume of a solution of known concentration consumed during analysis is taken as the amount of active constituent in the sample.
• Titrant


  Aka Volumetric solution/ Standard solution. Reagent of known concentration.
• Titrand


  Aka Analyte/ Active constituents. Sample being analyzed.
• Indicators


  Compounds capable of changing colors near or at the end point.
• Equivalence Point


  Theoretical point at which equivalent amounts of the analyte and titrant have reached. N1V1 = N2V2 or M1V1 = M2V2. Molarity is used when the stoichiometric ratio between titrant and analyte is 1:1.
• End Point


  Actual point at which equivalent amounts of the analyte and titrant have reacted. Point where a physical change occurs that is associated with the condition of chemical equivalence.
• Standardization


  Process of determining the exact concentration of a solution.
• Primary Standard


  Substance of high degree of purity. Serves as a reference material (standard) in titrations. Used in direct standardization purposes.
• Secondary Standard


  Standard solutions whose purity has been determined by chemical analysis. Used in indirect standardization purposes.
• Important requirements for a Primary Standard


  • High purity
  • Atmospheric stability
  • Absence of hydrate of water
  • Modest cost
  • Reasonable solubility in titration medium
  • Reasonably large molecular weight
• Equivalence Factors (F)


  Number of reacting entities per reagent.
• Equivalence Factors for Acids


  • HCl: f = 1
  • H2SO4: f = 2
  • CH3COOH: f = 1
  • H3PO4: f = 2*
  • H3BO3: f = 1*
• Equivalence Factors for Bases


  • Na(OH): f = 1
  • Mg(OH)2: f = 2
  • Al(OH)3: f = 3
  • NH3: f = 1
• Equivalence Factors for Salts


  • NaCl: f = 1
  • MgO: f = 2
  • MgSO4: f = 2
  • Ca3(PO4)2: f = 6
• Equivalence Factors for Oxidizing Agents


  • Permanganate: MnO4- -> Mn2+, f = 5
  • Dichromate: Cr2O72- -> Cr3+, f = 6
  • Bromate: BrO3- -> Br-, f = 6
  • Ceric: Ce4+ -> Ce3+, f = 1
  • Iodine: I2 -> I-, f = 2
• Equivalence Factors for Reducing Agents


  • Ferrous: Fe2+ -> Fe3+, f = 1
  • Oxalate: C2O42- -> CO2, f = 2
  • Thiosulfate: 2S2O32- -> S4O62-, f = 2
  • Arsenite: AsO2- -> As3+, f = 2
  • Titanous: Ti3+ -> Ti4+, f = 1
• Direct Titration


  1 titrant/VS
• Residual Titration


  2 titrant/VS. Also called Back titration. 1st VS added in excess, 2nd VS used to titrate the excess (unreacted) 1st VS.
• Classification of titrations based on reactions involved


  • Acid-Base (Neutralization)
  • Oxidation-Reduction (Redox)
  • Complexation
  • Precipitation
• Acidimetry


  Measurement of a base by a standard acid.
• Alkalimetry

  Measurement of an acid by standard base.
• Indicators used in aqueous acid-base titrations


  • SA + SB = Phenolphthalein, Methyl red/orange
  • WA + SB = Phenolphthalein
  • WA + SA = methyl red/ orange
  • WA + WB = not employed
• Indicators used in non-aqueous acid-base titrations


  • Non-aqueous Acidimetry - Crystal violet
  • Non-aqueous Alkalimetry - Thymolthalein, Thymol blue, Azoviolet
• Reagents used in aqueous acidimetry and alkalimetry


  • Acidimetry: VS - HCl/ H2SO4, 1° std - Na2CO3, TRIS/THAM, 2° std - NaOH VS

  Alkalimetry: Direct - NaOH, KOH, Ca(OH)2, NaHCO3, Residual - ZnO, NaKC4H4O6, Special Tech - Double indicator for mixed alkali
• Reagents used in non-aqueous acidimetry and alkalimetry


  • Acidimetry: VS - HClO4 (perchloric acid)

  Alkalimetry: VS - HClO4 (perchloric acid)
• Classification based on the Reactions involved


  • Acid-Base (Neutralization)
  • Oxidation-Reduction (Redox)
  • Complexation
  • Precipitation