Pharmaceutical Analysis

Typical Pharmaceutical Analysis

5/9/2015 ACI Limited, Md. Saddam Nawaz 1

Analytical Technologies

Spectroscopy (UV-Visible)

Chromatography (liquid Chromatography)

Titrimetric Analysis (Classical and Automated)


UV-Visible Spectroscopy


Theory/Principle of Spectroscopy


A Typical UV-Vis

Spectrophotometer


Beer-Lambert Law


Instrumentation


Analytical Spectra


Calibration

Wavelength Accuracy

Absorbance Accuracy

Stray Light

Resolution


Applications

Assay

Characterization

Identification

Dissolution Assay

Dissolution Kinetic Study5/9/2015 ACI Limited, Md. Saddam Nawaz 10

Chromatography

Column Chromatography

Planer Chromatography

Super Critical FluidChromatography

Chromatography

Gas Chromatography Liquid Chromatography

High PerformanceLiquid Chromatography


Liquid Chromatography (LC) Laboratory


Instrumentation

Reservoir

PumpInjector

Column Detector

Data Processor

Low pressure gradient valve


A Typical HPLC


HPLC Columns


Column Selections

Luna, ODS-AQ, xTerra, Symmetry, Nucleosil, ProC18, Stable bond (low pH), Stable bond

extended (high pH)

Molecular weight < 2,000 Da

Organic Soluble

Aqueous soluble

Hexane

MethanolAcetonitrile

THF

Non-Ionic

Ionic

Peptides Proteins

Normal Phase

Reversed Phase

Reversed Phase

Reversed Phase

Reversed Phase

Reversed PhaseLuna, ODS-AQ

Luna, xTerra, Symmetry, Nucleosil, Stable bond (low pH),

Stable bond extended(high pH)


Solvents for HPLC

0.010.20.891.33Water

3.15.80.341.34190Acetonitrile

3.05.10.541.33205Methanol

3.64.31.081.36210Ethanol

3.54.81.201.42215Dioxane

4.44.00.461.40212THF

4.23.90.821.38205Isopropanol

3.90.701.40210n-Butanol

3.10.421.42233Dichloromethane

2.70.321.50280Benzene

2.40.291.49285Toluene

2.10.251.40220n-Butyl ether

0.20.401.39200Heptane

0.10.301.37190Hexane

Solvent

Strength

for RPC

Polarity

(p)

Viscosity

(cP,25oC)

Refract.

index

UV

Cutoff

(nm)

Solvent


Buffer for HPLC

20010.3 – 12.311.3Pyrrolidine

20010.0 – 12.011.0Triethylamine*

2057.3 – 9.38.3Tris

4.4 – 6.45.4

3.7 – 5.74.7

2302.1 – 4.13.1Citrate

2103.8 – 5.84.8Acetic acid*

2102.8 – 4.83.8Formic acid*

11.3 – 13.312.3

6.2 – 8.27.2

2001.1 – 3.12.1Phosphate

UV Cutoff(nm)

Buffer capacity

pKaBuffer

*Volatile buffers5/9/2015 ACI Limited, Md. Saddam Nawaz 18

Chromatogram


Separation Technique


System Suitability Test (SST)

Repeatability, %RSD (CV)

Capacity factor, K’

Selectivity/Relative Retention Time

Theoretical Plates, N (Efficiency)

Resolution

Asymmetry/Tailing Factor


Repeatability, CV (%RSD)

X=(X1+X2……..Xn-1+Xn)/n

N=Number of Analysis

X1…..Xn: Retention time (or area or heights)

X = Average

C.V : Coefficient of Variation5/9/2015 ACI Limited, Md. Saddam Nawaz 22

Capacity Factor, K’


Selectivity/Relative Retention Time,


Theoretical Plate


Resolution


Tailing Factor, T

T=W0.05/2f


Calibration

Solvent Delivery Unit (LC-20 AD) Stability Test

Flow Rate Accuracy Check

D2 Lamp Test

W Lamp Test

Wavelength Accuracy Test

Inject Volume Accuracy Test

Gradient Concentration Test (Low Pressure Gradient System)

Noise/Drift Test5/9/2015 ACI Limited, Md. Saddam Nawaz 28

Applications

Assay

Identification

Impurity Analysis

Dissolution Assay


Titrimitric Analysis

Classical

Modern


Advantages

There are several reasons why titration is used in laboratories worldwide:

Titration is an established analytical technique

It is fast

It is versatile

It is a very accurate and precise technique

(Reproducibility <1%, precision 0.1% achieved)

A high degree of automation can be implemented

Economical compared to more sophisticated techniques

It can be used by low-skilled and low-trained operators


TitrantsThe titrants should be selected, The exact concentration of the titrant

is determined periodically and indicated as its titer. The titer should be stable. It is determined with the aid of primary standards.


Titration media


Overview of the different titration techniques


Different titration techniques

Indication principles Chemical reactions Applications

Potentiometry: The concentration-dependent potential (mV) of a solution is measured against a reference potential

• Aqueous acid/base titrations• Non-aqueous acid/base titrations • Redox titrations• Precipitation titrations

Content determination of pharmaceutical constituents

Acid content in fruit/vegetable juices, wine, milk, vinegar

Voltametry: The concentration dependent potential of a solution (mV) is measured at a constant electric current

• Karl Fischer Water in butter

Water in oil or gasoline

Bromine number or index of gasoline

Amperometry: The current flowing through a sample solution (μA) is measured at a constant potential

• Amperometrictitration

Iron(II) determination

Vitamin C determination


Different titration techniques

Indication principles Chemical reactions

Applications

Photometry: The light transmission (mV or % transmission) of a coloured or turbid solution is measured with a photometric sensor

• Complexometry

• Turbidimetry

Total hardness of water

Two-phase surfactant titration

Conductivity: The change of conductivity during a titration is measured with a conductivity sensor connected to the conductivity board of an Excellence titrator

• Conductometrictitration

Sulphate content by precipitation with Barium


Schematic representation of the different steps

in a titrator method


Endpoint titrations (EP) &

Equivalence point titrations (EQP)


Recording the titration curve


Evaluation principles

symmetric curve asymmetric curve

minimum/maximum curvesegmented curve (1st derivative)

segmented curve (2nd derivative)5/9/2015 ACI Limited, Md. Saddam Nawaz 40

Potentiometric indication


Potentiometric titrations in non-aqueous solvents

Solvotrode5/9/2015 ACI Limited, Md. Saddam Nawaz 42

(Bi)amperometric and (bi)voltametric indication


Photometrically indicated titrations


Validation of Titration Methods

Accuracy,

Precision

Trueness


Types of errors

Systematic errors

Random errors

Gross errors


Analytical Method Validation Parameters

Precision

Repeatability

Intermediate Precision

Accuracy

Linearity and Range

Specificity

Sensitivity (LOD and LOQ)

Robustness

Ruggedness5/9/2015 ACI Limited, Md. Saddam Nawaz 47

THANK YOU


Pharmaceutical Analysis

Documents

Transcript of Pharmaceutical Analysis