1 - Introduction

Question 1

What does analytical chemistry deal w/?

Answer 1

• Physical properties
• Chemical properties
• Purity
• Content
• Stability
• And quality of a chemical compound

Question 2

Pharmaceutical analysis is analytical chemistry w/ focus on ____

Answer 2

Pharmaceutical products

Question 3

Accuracy definition

Answer 3

• Degree of conformity w/ a standard

- Commonly expressed as mean (accuracy) +/- SD (precision)

Question 4

Precision definition

Answer 4

Degree of perfection in an instrument and/or method that is used to obtain a result

Question 5

Repeatability definition

Answer 5

• Precision under the same operating conditions over a short period of time
• Sometimes also called intra-assay precision
• Could indicate either within-day precision or between-day precision of a method or an operator

Question 6

Reproducibility definition

Answer 6

• Precision among different labs, from using the standard operating procedures (SOPs)
• Can be within-lab or between-lab reproducibility
• Pharmacopeial monographs (ex: USP) are regarded as official quality control SOPs
• Pharmaceutical manufactures often create their own SOPs for internal quality control purposes during the production of a dosage form

Question 7

Analytical blank definition and example

Answer 7

• Composed of all reagents or solvents used in an assay w/o any analyte being present
• True analytical blank should reflect all the operations to which the analyte in a real sample is subjected
• Ex: a chromatographic mobile phase can be used to reconstitute an analyte to minimize interference from other components

Question 8

Calibration definition and example

Answer 8

• Involves comparison of the value/values of a particular parameter measured by the system under strictly defined conditions w/ preset standard values
• Most assay methods or instruments require regular calibration
• Ex: a calibration curve is constructed for an HPLC assay to calculate concentrations of the analyte

Question 9

Detection limit definition

Answer 9

• The lowest amount of analyte in a sample that can be detected but not necessarily quantitated as an exact value
• Done for an individual analytical procedure
• Signal of detection limit of an analyte is normally defined as 3x larger than that of the analytical blank
• True limit detection should reflect all the processes to which the analyte in a real assay is subjected & not be a simple dilution of a pure standard for the analyte until it can no longer be detected
• Chromatographic assays normally have lower detection limits than spectrophotometric assays

Question 10

Quantitation limit defition

Answer 10

• Lowest amount of analyte in a sample that can be quantitatively determined w/ suitable precision & accuracy
• Done for an individual analytical procedure
• Signal quantitation limit of an analyte is normally defined at 10x larger than that of the analytical blank or 3x larger than that of the detection limit

Question 11

Linearity and correlation coefficient definition

Answer 11

• Ability of an analytical procedure to obtain test results w/in a given range that are directly proportional to the concentration (or amount) of analyte in the sample
• Equation of linearity is normally obtained by linear regression of a series of plots & takes the form of y = mx + b
• Correlation coefficient indicated how close the calculated values are to the actual values used in a calibration (in general, R > 0.99 is considered satisfactory for assay calibration)

Question 12

Range definition

Answer 12

• For an analytical procedure, is the interval between the upper and lower concentration (or amount) of analyte in the sample
• Sample concentrations must be adjusted appropriately beforehand by dilution or concentration so that they fall into the range of the equipment used to make the measurement

Question 13

Robustness definition and example

Answer 13

• Ability of an analytical procedure to remain unaffected by small, but deliberate variations in experimental parameters
• Provides indication of reliability during normal application
• Ex: changes of instrumentation, slight variations in extraction procedures, sensitivity to minor impurities in reagents

Question 14

Selectivity definition

Answer 14

• How capable a method is of measuring the analyte alone in the presence of other compounds contained in the sample
• Fluorescence spectrophotometry is more selective than UV/visible spectrophotometry b/c fewer compounds exhibit fluorescence
• Fluorescence assays may be less robust than UV/visible assays b/c they use more complex principles & therefore more prone to method variations

Question 15

Sensitivity definition

Answer 15

How responsive it is to a small change in the concentration of an analyte