PHRM- OVERVIEW OF DRUG ANALYSIS

OVERVIEW OF DRUG ANALYSIS

pharm analysis mostly refers to

lab based evaluation of drugs and associated substances inc drug formulation or dosage form

involves drug analyte assessment in a sample of

bulk/unformulated drug substance

drug formulation/ dosage form

biological medium

purpose of pharm analysis assay can be

QUANTITATIVE

determination of amount of analyte within sample

QUALITATIVE

determination of presence and or ID of the analyte in sample

type of analytical/assay tech for drug analysis dependent on

purpose

nature of drug

properties like-

solubility, ionisability, acid-base nature, stability and spectral features

for drug formulation and biosample analysis, method of choice dependent on

type of dosage form

biomedium

assay quality

simplicity

cost/availability of eq/reagents and analyst skills set

DRUG SAMPLE USUALLY NEEDS FURTHER PROCESSING TO PRODUCE AN AQ SOLUTION FOR ANALYSIS

wide variety of analytical tech are available

titrimetry

spectrophotometry

HPLC

mass spectrometry

fluorimetry

HPCE

NMR spectroscopy

IR spectroscopy

Analysis of drug substances

pre-formulation

QUANTITATIVE analysis of drug compound

inc titrimetry and spectrophotometry

QUALITATIVE analysis for verification of drug ID

assay methods- rapid and simple

major app areas for drug substance analysis are

QUALITY ASSURANCE/CONTROL

drug discovery and dev

determination of drug properties

Drug Percentage Purity

measure actual drug amount/mass in drug sample and compare to mass of sample used for assay

range 95%-105%

Drug percentage purity formula

impurities represent

trace substances

H2O

salts

Assay for drug substances- 3 stage procedure

sampling

random selection of a representative portion or units from drug sample/batch for appraisal purposes

sample prep

pre-analysing treatment/processing of assay sample to produce suitable form to analyse

may inc drug isolation/separation and purification procedures

sample analysis

app of assay tech to obtain desired drug data

Assay for drug substances

selection of small drug quantity by MASS <0.5g

NOT need lengthy sample prep

NEED PREP OF SAMPLE SOLUTION FOR ANALYTICAL PURPOSES

Assays for drug substances part 2

prep of drug solution involves solvation/dissolution of specified drug mass- assay sample- in specified vol of solvents and or reagent solution

solvents used are-

H2O

OH- EtOH

reagent solutions-

dilute aq acids and bases like HCl or NaOH

used to dissolve acidic/basic drugs

key quality assessment criteria for assay inc

ACCURACY

closeness of true value

PRECISION

closeness between series measurements obtained

Quality of pharm assays have 3 levels

repeatability/ intra-assay precision

needs to be precise on separate days for same analyst and assay conditions

over short time

same analyst

intermediate precision/within lab reproducibility

in lab reproducibility

same lab conditions

different analysts

different days

reproducibility/ between lab reproducibility

precision between different analysts in diff labs

transferred to another part of company

Other important assay quality/validation parameters

robustness

measure capability of assay to cope with subtle change in procedure/conditions

specificity/ selectivity

measure assay by ability to detect analyte alone or with other substances

alone is selective, analyte with other substance is non-selective

range

limits of analyte can be accurately/precisely measured by assay

sensitivity

measure assay responsiveness to small variations in analyte amount or conc

high assay sensitivity means can measure extreme low analyte levels