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Table 2 Advantages and disadvantages of ultraviolet spectrophotometric methods for the determination of the minor component presented in different fixed-dose pharmaceutical combinations

From: Ultraviolet spectrophotometric methods for the determination of the minor component presented in fixed-dose pharmaceutical combinations through the last two decades (2000–2020)

Methods

Advantages

Disadvantages

Methods based on signal enhancing

 Zero-crossing derivative

-Raises resolution of overlapped spectra in binary mixture.

-Amplifies signal to noise ratio.

-Demands choosing a suitable wavelength increment for proceeding derivative

-Demands selecting zero-crossing point.

 Area under the curve correction

-Raises sensitivity, more than absorption correction method

-Easier calculations than traditional (AUC)

-Requires extended spectrum of one of the components than the other.

Chemometric methods

 Continuous wavelet transform as a pre-processing tool in partial least-squares

Collects more analytical data from the full matrix spectrum of drugs mixture tested, enabling each component in the mixture to be calculated successfully.

Several steps were required to complete the separation process successfully.

The need to special software (Matlab)

 Partial least-squares (PLS)

In PLS, both the data in the absorption matrix and the concentration matrix are used and this provides a more stable model as it eliminates noise from both absorption and concentration data.

Need Matlab program connected with UV-spectra device

 Partial least squares with regression model updating

Considered as a robust analytical method despite spectral data noise and missing data.

Need Matlab program connected with UV-spectra device

 Artificial neural networks (ANN)

Obtaining the relationships between independent variables, allowing all drugs to be calculated in extended nonlinear range.

Need Matlab program connected with UV-spectra device

Methods based on geometrical relationship of standard addition

 H-Point standard addition

-Determines binary mixture with large difference in its components signal

-Required choosing two wavelengths where the interfering component has the same absorbance

-Many graphical representations and

tests are needed

 Ratio H-point standard addition

-Determines binary mixture with large difference in its components signal

-No need for any considerations upon selecting the wavelengths

-Required normalized spectrum for division

 Geometrical amplitude modulation

-Applicability to partial and sever overlapped spectra

-The need ofiso-absorption point or extended spectrum of the major component.

-The need of normalized spectrum for division

-Many tests are needed.

 Geometrical induced amplitude modulation

-Applicability to partial and sever overlapped spectra

-No need for iso-absorption point or extended spectrum of the major component.

The need of normalized spectrum for division

- Many tests are needed

Methods based on geometrical relationship of standard addition

 Compensated area under the curve

-Determines binary mixture with large variance in its components signal

-Calibration curve is required for every mixture

 Derivative compensation ratio

-Determines binary mixture with large variance in its components signal

-Raises resolution of overlapped spectra in binary mixture

-Calibration curve is needed for every mixture

-Needs for choosing a suitable wavelength increment for proceeding derivative

Methods based on ratio spectra

 Ratio difference

Cancels derivative step which improve signal to noise ratio

-Requires tests to choose the best concentration for dividing.

-The need of standard spectrum of the interfering substance for the dividing process

 Ratio subtraction

-Regains the zero order spectra of the interfering substances

-Require extended spectrum of one of the components than the other

-Incapables to determine the extended component

 Derivative ratio–zero-crossing

-Applies to determine compounds in ternary mixture

-Requires tests to choose the best concentration for dividing.

-Needs standard spectrum of interfering substance for the dividing process

-Needs selecting zero-crossing point

 Derivative ratio

-Applies to determine compounds in ternary mixture.

-No necessity for zero-crossing point

-Requires tests to choose the best concentration for dividing

-Needs choosing a suitable wavelength increment for proceeding derivative

-Needs standard spectrum of the interfering substance for the dividing process.

 Double divisor ratio spectra derivative

-Applies to determine compounds in ternary mixture.

-No necessity for zero-crossing point

-Requires tests to choose the best concentration for dividing

-Needs choosing a suitable wavelength increment for proceeding derivative.

-Needs standard spectrum of the two interfering substances for the dividing process

 Area under curve of derivative ratio

-Cancels interference of the major compounds

-Raises sensitivity

-Requires tests to choose the best concentration for dividing

-Needs standard spectrum of the interfering substance for the dividing process

 Successive derivative of ratio spectra

-Applies to determine compounds in ternary mixture

-Requires extended spectrum of one of the components

in the ternary mixture

- Requires tests to choose the best concentration for dividing.

-Needs standard spectrum of the interfering substance for the dividing process

 Extended ratio subtraction

-Regains the zero order spectra of the interfering substances

-Requires extended spectrum of one of the components

-Un appropriates for determining low concentrations of the more extended substance

-Needs standard spectrum of the none extended substance for the dividing processspectrum as a divisor

-Requires tests to choose the best concentration could be used as a divisor

 Constant center

-Regains the zero order spectra of the interfering substances

-Applicability to partial and sever overlapped spectra

-Needs standard spectrum of the interfering substance for the dividing process

-Requires tests to choose the best concentration for dividing

 Amplitude modulation

-Eliminates the step of selecting the best divisor concentration.

-Getting the concentration of both substances by one regression equation

-Requires extended spectrum of one of the components

-The need of normalized spectrum for dividing process

 Absorption subtraction

-Getting the concentration of both substances by one regression equation

-Demands the calculation of absorption factor.

 Amplitude summation

-The drafts in the isosbestic point in derivative step may able to correct interference from some additives

-Demands the calculation of response factor.

-Amplifies signal to noise ratio.

-Requires choosing a suitable wavelength increment for proceeding derivative

 Absorptivity centering

-Regains the zero order spectra of the interfering substances

-Applicability to partial and sever overlapped spectra

-Demands the calculation of two factors

-The need of normalized spectrum for dividing process

-Requires many steps to apply it

 Derivative subtraction coupled with constant multiplication

-Regains the zero order spectra of the interfering substances

-Requires extended spectrum of one of the components

-Requires tests to choose the best concentration for dividing

 -Constant multiplication coupled with spectrum subtraction

-Regains the zero order spectra of the interfering substances

-Require extended spectrum of one of the components

-Requires standard solutions of the interfering compound to be used as a divisor.

-Requires tests to choose the best concentration could be used as a divisor

 Constant center coupled with spectrum subtraction

-Regains the zero order spectra of the interfering substances

-Applicability to partial and sever overlapped spectra

-Requires standard solutions of the interfering compound to be used as a divisor.

-Requires tests to choose the best concentration for dividing

 Mean centering

The transformed signals are evaluated at the highest peak point, for optimum maximum sensitivity, levels

De-noising and raising the signal to noise ratio

Coding of algorithms (special sequence in Matlab®)

 Continuous wavelet transform

Many different wavelets family are often used for CWT analysis as they allow the separation of phase and amplitude components associated with the signal.

Several experiments were required to find the suitable wavelet family to complete the separation process successfully

Methods based on sample enrichment by sample spiking (standard addition ) or spectrum addition technique

 Sample spiking (standard addition)

-Determines low concentration of minor component when eviating from Beer’s law

Depending on one standard added for determination

 Spectrum addition

-Determines low concentration of minor component when deviating from Beer’s law

-More accurate results comparing to sample spiking (standard addition)

-Depending on one standard spectrum for determination.