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• 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
• Types of 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, 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. 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. Absolute Error: E = |X1 - X2|. Relative Error: ER = |X1 - X2| x 100 / X2

  
• 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

  
• Mean


  Average or arithmetic mean. Obtained by dividing the sum of replicate measurements by the number of measurements in the set

  
• Median


  Middle result when replicate data are arranged in increasing or decreasing order. Less affected by extreme values (outliers)
• 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


  Aka Stoichiometric point. Theoretical point at which equivalent amounts of the analyte and titrant have reached. N1V1 = N2V2 or M1V1 = M2V2
• 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)


  • Acids: f = no. of replaceable H+
  • Bases: f = no. of replaceable OH
  • Salts: f = total (+) or (-) charges
  • Oxidizing Agents: f = no. e gained
  • Reducing Agents: f = no. e lost
• Classification of titrations based on reactions

  • 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 for aqueous acid-base titrations

  • SA + SB = Phenolphthalein, Methyl red/orange

  WA + SB = Phenolphthalein

  WA + SA = methyl red/ orange

  WA + WB = not employed
• Indicators for non-aqueous acid-base titrations

  • Non-aqueous Acidimetry – Crystal violet

  Non-aqueous Alkalimetry – Thymolthalein, Thymol blue, Azoviolet
• Examples of aqueous acidimetry

  • Direct: NaOH, KOH, Ca(OH)2, NaHCO3

  Residual: ZnO, NaKC4H4O6

  Special Tech: Double indicator for mixed alkali
• Examples of non-aqueous acidimetry

  • Direct: Methacholine, K acetate, Diphenoxylate Diazepam
• Examples of aqueous alkalimetry

  • Direct HCl, H2SO4, H3PO3, H3BO3
• Indicators


  Uses water as solvent
• Methyl red/orange


  Indicator for acid-base titrations, gives red colour in acidic solutions and yellow in basic solutions
• pH


  Measure of acidity or basicity of a solution
• Phenolphthalein


  Indicator used in aqueous acid-base titrations, gives pink/red colour in basic solutions
• Methyl red/orange


  Indicator used in aqueous acid-base titrations, gives red colour in acidic solutions and yellow in basic solutions