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A Review: GC Method Development and validation

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International Journal of Analytical and Bioanalytical Chemistry

Universal Research Publications. All rights reserved

ISSN-2231-5012
Review Article
A Review: GC Method Development and validation
Santosh Kumar Bhardwaja,b, K. Dwivedia and D. D. Agarwala
a
School of Studies in Chemistry, Jiwaji University, Gwalior-474011, Madhya Pradesh, India
b
Shimadzu Analytical India Pvt Ltd, Delhi, India.
Email: sbhardwaj81@yahoo.com
Received 16 January 2016; accepted 26 January 2016
Abstract
The intension of this paper is to review and discuss the various steps involved in GC method development and validation.
Gas chromatography is a sensitive, accurate, reproducible, quantitative and versatile tool well adapted for the analysis of
complex mixtures. This techniques plays an important role in analysis of drugs and pharmaceutical products. However the
use of GC is limited to volatile thermally stable compounds or the molecules that may undergo derivatization reactions to
thermally stable products. Method development and validation play important role in the discovery, development and
manufacture of pharmaceuticals. Method development is the process of proving that an analytical method is acceptable for
use to measure the concentration of an API in a specific compound dosage form which allow simplified procedures to be
employed to verify that an analysis procedure, accurately and consistently will deliver a reliable measurement of an active
ingredient in a compound’s preparation. The method validation is essential for analytical method development and tested
extensively for specificity, linearity, accuracy, precision, range, detection limit, quantitation limit, robustness and system
suitability.
© 2016 Universal Research Publications. All rights reserved
Keywords: GC, Method development, Validation

1.0 Introduction:
Gas chromatography is a unique and versatile technique. In
its initial stages of development it was applied to the
analysis of gases and vapors from very volatile
components. The work of Martin and Synge and then
James and Martin in gas–liquid chromatography (GLC)
opened the door for an analytical technique that has
revolutionized chemical separations and analyses. As an
analytical tool, GC can be used for the direct separation and
analysis of gaseous samples, liquid solutions, and volatile
solids. If the sample to be analyzed is nonvolatile, the
techniques of derivatization or pyrolysis GC can be
utilized. Gas chromatography is the analytical technique
used for product identification (under very controlled
conditions) and must be directly coupled to a
massspectrometer when information other than a
comparative fingerprint (program) is required, such as
positive identification of peaks on the chromatogram. 1The
basic principal of gas chromatography is that greater the
affinity of the compound for the stationary phase, more the
compound will be retained by the column and longer it will
be before it is eluted and detected. Thus the heart of the gas
chromatograph is the column in which separation of the
International Journal of Analytical and Bioanalytical Chemistry 2016; 6(1): 1-7
1
component takes place, and to this must be added the
source and control of the carrier gas flow through the
column, a mean of sample introduction and a means of
detection of the components as they elute from the end of
the column. Since temperature will influence the
volatility of the analytes, the column is placed in a
thermostatically controlled oven. 2Unlike most other types
of chromatography, the mobile phase does not interact with
molecules of analyte but only transport the analyte through
the column3. Faster gas chromatographic separation is a
generally beneficial option. Since the decrease time of
analysis results in the increased sample throughput and
consequently, the laboratory operation costs can be reduced
significantly. Reduction of analysis time can be achieved
by changing column parameters (shorter length, smaller
column inner diameter, thinner film of stationary phase) or
operational parameters (faster temperature program rate,
isothermal analysis. Different carrier gas, higher carrier gas
flow rate or a combination of both approaches can be
applied.4A basic gas chromatograph is represented
diagrammatically in figure -1.
2.0 GC Method Development:
Methods are developed for new products when no official
 Schematic Diagram of Gas Chromatography

Steps involved in GC Method development

International Journal of Analytical and Bioanalytical Chemistry 2016; 6(1): 1-7

2
 Gas Chromatographic Method Validation
methods are available. Alternate method for existing (Non-
Pharmacopoeial) products are to reduce the cost and time
for better precision and ruggedness. When alternate method
proposed is intended to replace the existing procedure
comparative laboratory data including merit/demerits are
made available. 5Several steps are being considered for GC
method development like column selection (stationary
phase and dimensions: column id, length, and film
thickness), carrier gas selection (Nitrogen, Helium, flow
rate), temperature programing (Initial temperature, initial
hold, ramp rate, final temperature, and final hold), injector
tempreture and detector tempreture.6
Steps involved in Method development are.7
 Understanding the Physicochemical properties of
sample.
 Selection of chromatographic conditions.
 Developing the approach of analysis.
 Sample preparation
 Method optimization
 Method validation (figure-2)
2.1 Understanding the physicochemical properties of
sample:
Gas chromatography is a unique and versatile technique. In
its initial stages of development it was applied to the
analysis of gases and vapors from very volatile
components. The mixture to be separated and analyzed by
GC may be either a gas, a liquid, or a solid in some
instances.1Before beginning the GC method development,
it is important to review what is known about the sample.
The goal of the analysis should be defined at this point and
International Journal of Analytical and Bioanalytical Chemistry 2016; 6(1): 1-7
3
considerations must be given to the number of samples to
be analysed. 8Proper selection of the methods depends upon
the nature of the sample (volatile or nonvolatile molecule),
its molecular weight, solubility and melting point. 9As
much as possible informations should be gathered about the
samples including aggregation state, sample composition
(analytes, matrix, solvent), information on GC relevant
properties, such as boiling point range, polarity, functional
groups, solubility, reactivity, stability at room temperature
in the presence of air. It should need to be checked that,
does sample contain thermally or chemically labile
components, aggressive substances (acid, bases), water or
nonvolatile residues, does the sample contain hazardous
substances, any special handling required.10If the sample to
be analyzed is nonvolatile, the techniques of derivatization
or pyrolysis GC can be utilized. This latter technique is a
modification where in a nonvolatile sample is pyrolyzed
before it enters the column.8
2.2 Selection of chromatographic conditions
The initial choices of column and supporting
instrumentation have a profound influence on the
possibilities for, and ultimate results of, separation
optimization. Manipulation of column parameters
(stationary phase, inner diameter, length, and film
thickness) gives chromatographers control over column
efficiency, resolution and speed of analysis.1 In gas
chromatography, the elution order of analytes is governed
by several factors such as latent vapour pressures,
solubilities in stationary phase, and propensities for
molecular interaction in the stationary phase. All of these
effects change with temperature and their concerted effect
ultimately determine the equilibrium distribution of solute
molecules between the mobile and stationary phase.11
2.2.1 Selection of Column:
A column is of course, the starting and central piece of a
chromatograph. An appropriately selected column
can produce a good chromatographic separation which
provides an accurate and reliable analysis. An improperly
used column can often generate confusion, inadequate, and
poor separations which can lead to results that are invalid
or complex to interpret. There are over 10,000 compounds
that can be analysed by GC and over 400 GC capillary
columns. It is a challenge for a column manufacturer to
give detailed column selection guidelines to meet such a
wide variety of applications.12An optimized
chromatographic separation begins with the column. The
selection of the proper capillary column for any application
should be based on four significant factors which are
stationary phase, column internal diameter, film thickness,
and column length. The differences in the chemical and
physical properties of injected organic compounds and their
interactions with stationary phase are the basis of
separation process. When strength of the analyte-phase
interactions differs significantly for two compounds, one is
retained longer than the other. How long they are retained
in the column (retention time) is a measure of these
analyte-phase interactions. Changing the chemical features
of the stationary phase alters its physical properties. Two
compounds that co-elute (do not separate) on a particular
stationary phase might separate on another phase of
different chemistry.12
2.2.2 Selection of Carrier Gas: Several inert gases can be
used as the carrier gas or mobile phase of GC. Hydrogen,
helium and nitrogen are all common carrier gases. Each
carrier gas has its benefits and systems for which it is best
suited.13The choice of gas to be used as mobile phase in gas
chromatography is influenced by the following
requirements and considerations.2
Inertness
Dryness
Freedom from oxygen
Safety
Cost
Availability
2.2.3 Optimization of Column oven temperature
program
The column resides in an oven, and temperature, which
greatly affects the effectiveness of the chromatographic
separation, is an extremely important factor used in
controlling GC. In many cases, isothermal is not the most
effective temperature mode for sample separation; in such
cases, a temperature program can be used. Most GC
temperature program have initial temperature, a ramp
(degree increase per minute) and a final temperature.Using
a linear temperature program as a starting point if previous
analysis information is not available to use as aguide, the
first program development step is to try a simple, linear
temperature program. To improve the resolution of earlier
eluting peaks, decrease the initial temperature or increase
the initial hold time. Decreasing the initial temperature
usually results in the largest resolution improvement, but
International Journal of Analytical and Bioanalytical Chemistry 2016; 6(1): 1-7
4
analysis times are substantially increased. The resolution of
peaks eluting in the middle of the chromatogram can be
altered by change in ramp rate. If there is excessive peak
resolution, the ramp rate can be increased to reduce
resolution and the analysis time. If there is insufficient
resolution, decrease the ramp rate, but there will be an
increase in the analysis time. Better resolution of later
eluting peaks often occurs when decreasing the ramp rate.
Another option to alter resolution of peaks in the middle of
a chromatogram is to use a mid-ramp hold. A mid ramp
hold is a several minute isothermal portion somewhere
during a temperature ramp. Stop the temperature program
shortly after last peak has eluted from the column. If
column’s isothermal temperature limit is reached and peaks
are still eluting, a final hold time is necessary. Only use a
final hold time if the temperature limit is reached.12,13
2.2.4 Optimization of Injector type, temperature &
injection volume
Introduction of the sample into GC system is a critical step
in separation. The reproducibility of the amount of sample
injected is important to ensure the reproducibility of results.
A sample can be injected manually into the system or by
using an auto sampler system. A major errors in GC is poor
injection technique. The injector temperature for
separation. The temperature of injector is used to rapidly
vaporize the liquid sample into gaseous phase that can be
carried to the column for separation. In capillary and micro
packed gas chromatography (GC), there are four primary
techniques for vaporizing a sample and transferring it onto
the inlet of the analytical column: split, splitless, direct, and
on-column injections. Of these, split and splitless injections
are the most commonly used techniques. Split Injector was
selected for analysis of sample with high concentration
levels. In the split injection mode, only a fraction of the
vaporized sample is transferred onto the head of the
column. The remainder of the vaporized sample is removed
from the injection port via the split vent line. Split
injections should be used only when sample concentrations
are high enough to allow a portion of the sample to be
discarded during the injection process, while still
maintaining a sufficient concentration of analytes at the
detector to produce a signal.13,14
2.2.5 Optimization of detector type & detector
temperature.
A variety of detector is commercially available to be used
with GC, each having its own limitations and advantages.
The most commonly used detector in GC is flame
ionization detector. FID is typically used for organic
compounds and used in quality control analysis of
pharmaceutical compounds. Detector temperatures and the
relative flow rates of carrier gas, hydrogen and air into the
detector are the key operating parameters. 13a series of
standards is defined for evaluation of detector parameters
such as drift, noise, sensitivity, linear range, dynamic range
etc. The variation in detector response with flow rate
depends on whether the detector is concentration or mass
flow dependent. For concentration dependent detectors
(e.g., thermal conductivity detector, photo ionisation
detector) a decrease in the flow-rate does not affect the
peak height, which remains approximately constant.
However the peak width, and consequently the peak area,
increase. In contrast, for mass flow detection systems (e.g.,
flame ionization detection, flame photometric detection,
nitrogen phosphorus detection) the response is inversely
proportional to the retention time. Therefore, any change in
chromatographic conditions which cause a change in the
retention time will also affect the peak height. It follows
that a decrease in the flow-rate results in reduced peak
heights, however the peak area remains approximately
constant.15
2.3. Developing the approach for analysis:
Two general approaches to GC method development can be
followed, either start from scratch or scale a current
method. The path that is taken depends on the status of the
current method. Method translation yields a scaled version
of the current method. If the current method meets all of the
analytical needs except speed, then translation is the best
way to go (especially if the analysis involves many
components). If there are deficiencies with the current
method, It might be better to redevelop the method from
scratch in orderto better meet the overall analytical
requirements.14 Proper selection of the methods depends
upon the nature of the sample (volatile or nonvolatile
molecule), its molecular weight, solubility and melting
point.9factors that affect gas chromatographic analysis are
column temperature, carrier gas flow-rate, injection
temperature, split ratio, detector temperature and sample
size.15All of these parameters are selected on the basis of
trials and followed by considering the system suitability
parameters. Typical parameters of system suitability are
e.g. retention time should be more than 5 min, the
theoretical plates should be more than 2000, the tailing
factor should be less than 2, resolution between 2 peaks
should be more than 5, % R.S.D. of the area of analyte
peaks in standard chromatograms should not be more than
2.0 % like other.16
2.4 Samplepreparation:
The sample that is injected into the gas chromatograph
following sample preparation must be either a liquid or a
gas, the analytes must be volatile enough under the
conditions of the inlet and column to traverse the
instrument, and, ideally, the matrix interferences must also
be volatile, so as not to contaminate the instrument or
column. In most cases, liquid samples must be dissolved in
a volatile organic solvent. The basic goal of sample
preparation is to ensure that these conditions are met, with
additional goals that the preparation be reproducible to
meet quantitative analysis requirements and straight
forward to perform, if the analysis is to be performed
routinely, as in quality assurance and in other routine
testing laboratories.1Before beginning the GC method
development, it is important to review what is known about
the sample. The goal of the analysis should be defined at
this point and considerations must be given to the number
of samples to be analyzed, available equipment, etc. The
nature of the sample (e.g. whether it is hydrophilic or
hydrophorbic, whether it contains protolytic functions, etc)
determines the best approach to method development.
Some samples require a pre-treatment prior to analysis
because of the need to remove interferences or to
International Journal of Analytical and Bioanalytical Chemistry 2016; 6(1): 1-7
5
concentrate sample analytes. The sample pre-treatment
development can at times be more complex than the
separation itself. The goals of the separation should be
specified at the beginning of the method development.
Moreover, before the sample is injected during the GC
method development, the detector should be selected to be
sensitive to all sample components of interest. The final
procedure should meet all the goals that have been defined
at the beginning of the method development and when the
method for quantitative use is finalized it should be
validated.8
2.5 Method optimization :
Several steps are involved in method development and
validation. In the case of analytical procedures like GC ,
these steps might include review of information on samples
to be analyzed, definition of separation goals; assurance of
special procedure requirements, sample pretreatment if any;
detector selection and setting, separation conditions
optimization, check for problems or special procedure
requirements, recovery of purified material, quantitative
calibration and qualitative method development.8The
experimental conditions should be optimized to get desired
separations and sensitivity after getting appropriate
separations. This will be achieved through
planned/systemic examination of parameters.16 During
optimization one parameter is changed at a time and set of
conditions are isolated rather than using a trial and error
approach.17
2.6 Method Validation :
Validation is derived from Latin from which means “strong
ness”. Validation is the strength or strongness of a
procedure, process, and capability of an equipment to
operate and is proved for its acceptability with confirmation
and documented legally on the basis of scientific
data.17Validation of an analytical method is the process by
which it is established by laboratory studies, that the
performance characteristics of the method meet the
requirements for the intended analytical application.
Validation is required for any new or amended method to
ensure that it is capable of giving reproducible and reliable
results, when used by different operators employing the
same equipment in the same or different laboratories. The
type of validation program required depends entirely on the
particular method and its proposed applications.13Results
from method validation can be used to judge the quality,
reliability and consistency of analytical results; it is an
integral part of any good analytical practice. Use of
equipment that is within specification, working correctly
and adequately calibrated is fundamental to the method
validation process. Analytical methods need to be validated
or revalidated.18 (figure-3)
• Before their introduction into routine use;
• Whenever the conditions change for which the method
has been validated
• Whenever the method is changed
Typical parameters recommended by FDA, USP, and ICH
are as follow.18-20
1. Specificity
2. Linearity & Range
3. Precision
  Method precision (Repeatability)
 Intermediate precision (Reproducibility)
4. Accuracy (Recovery)
5. Solution stability
6. Limit of Detection (LOD)
7. Limit of Quantification (LOQ)
8. Robustness
9. System suitability
Specificity:specificity of an analytical method as its ability
to assess unequivocally the analyte in the presence of
components, which may be expected to be present. It can
also be defined as ability of method to measure accurately
an analyte in the presence of interference, such as synthetic
precursors, excipients, enantiomers, and known (or likely)
degradation products that may be expected to be present in
the sample matrix.19
Linearity and range:The linearity of an analytical
procedure is its ability (within a given range) to obtain test
results, which are directly proportional to the concentration
of analyte in the sample. A linear relationship should be
evaluated across the range of the analytical procedure. It is
demonstrated directly on the drug substance by dilution of
a standard stock solution of the drug product components,
using the proposed procedure. Linearity is usually
expressed as the confidence limit around the slope of the
regression line.20 For the establishment of linearity,
minimum of five concentrations are recommended by ICH
guideline. The range of an analytical method is the interval
between the upper and lower levels that have been
demonstrated to be determined with precision, accuracy
and linearity using the method.21,22
Precision: The precision of an analytical procedure
expresses the closeness of agreement (degree of scatter)
between a series of measurements obtained from multiple
sampling of the same homogeneous sample under the
prescribed conditions. Precision may be considered at three
levels: repeatability, intermediate precision and
reproducibility. It can also be defined as degree of
agreement among individual test results when method is
applied repeatedly to multiple sampling of a homogeneous
sample. 20The precision of an analytical procedure is
usually expressed as the standard deviation or relative
standard deviation of series of measurements. Precision
may be either the degree of reproducibility or of the
repeatability of the analytical procedure under normal
conditions. Intermediate precision (also known as
ruggedness) expresses within laboratories variations, as on
different days, or with different analysts or equipment
within same laboratory. Precision of an analytical
procedure is determined by assaying a sufficient number of
aliquots of a homogeneous sample to be able to calculate
statistically valid estimates of standard deviation or relative
standard deviation.21
Accuracy (Recovery) : The accuracy of an analytical
procedure expresses the closeness of agreement between
the value which is accepted either as a conventional true
value or an accepted reference value and the value found. It
is determined by applying the method to samples to which
known amounts of analyte have been added. These should
be analysed against standard and blank solutions to ensure
International Journal of Analytical and Bioanalytical Chemistry 2016; 6(1): 1-7
6
that no interference exists. The accuracy is then calculated
from the test results as a percentage of the analyte
recovered by the assay. It may often be expressed as the
recovery by the assay of known, added amounts of
analyte.19-21
Solution stability: During validation the stability of
standards and samples is established under normal
conditions, normal storage conditions, and sometimes in
the instrument to determine if special storage conditions are
necessary, for instance, refrigeration or protection from
light.19
Limit of Detection (LOD) : Limit of detection (LOD) of
an individual procedure is the lowest amount of analyte in a
sample that can be detected but not necessarily quantitated
as an exact value. In analytical procedures that exhibit
baseline noise, the LOD can be based on a signal-to-noise
(S/N) ratio (3:1), which is usually expressed as the
concentration of analyte in the sample. The signal-to-noise
ratio is determined by: s = H/h Where H = height of the
peak corresponding to the component. h = absolute value of
the largest noise fluctuation from the baseline of the
chromatogram of a blank solution.20-22
Limit of Quantification (LOQ) : The limit of Quantitation
(LOQ) or Quantitation limit of an individual analytical
procedure is the lowest amount of analyte in a sample that
can be quantitatively determined with suitable precision
and accuracy. For analytical procedures such as HPLC that
exhibit baseline noise, the LOQ is generally estimated from
a determination of S/N ratio (10:1) and is usually
confirmed by injecting standards which give this S/N ratio
and have an acceptable percent relative standard deviation
as well.19-22
Robustness: is defined as the measure of the ability of an
analytical method to remain unaffected by small but
deliberate variations in method parameters (e.g. pH, mobile
phase composition, temperature and instrumental settings)
and provides an indication of its reliability during normal
usage. Determination of robustness is a systematic process
of varying a parameter and measuring the effect on the
method by monitoring system suitability and/or the analysis
of samples.19,20
System Suitability: System suitability tests are an integral
part of liquid chromatographic methods. They are used to
verify that the detection sensitivity, resolution and
reproducibility of the chromatographic system are adequate
for the analysis to be done. The tests are based on the
concept that the equipment, electronics, analytical
operations and samples to be analyzed constitute an integral
system that can be evaluated as such. Factors, such as the
peak resolution, number of theoretical plates, peak tailing
and capacity have been measured to determine the
suitability of the used method.19-22
3. Conclusion
In recent years development of the analytical methods for
identification, purity evaluation and quantification of drugs
has received a great deal of attention in the field of
separation science. This review describes GC method
development and validation in general way. A general and
very simple approach for the GC method development for
the separation of compounds was discussed. Knowledge of
the physiochemical properties of the primary compound is FID Method Development and Validation Parameters
of utmost importance prior to the any GC method for Analysis of Palm Oil (Elaeis guineensis Jacq.)
development. Severa lsteps are being considered for GC Fatty Acids Composition, Research in Plant Sciences,
method development like column section (stationary phase 2 (3) (2014), 53-66.
and dimensions: column id, length, and film thickness), 9. K.L. Dubal, V.R. Ram, G.J. Kher, P. N. Dave, H.S.
carrier gas selection (Nitrogen, Helium, flow rate), Joshi, Gas Chromatographic Method Development
temperature programing (Initial temperature, initial hold, and Validation of Assay Method for the
ramp rate, final temperature, and final hold), injector Determination of Ticlopidine Hydrochloride in
selection, Injector temperature, detector selection and Tablets Formulation, 1(3) (2013), 101-106.
detector temperature. Optimized method is also need to be 10. K.D. Wilde, W. Engewald, Practical Gas
validated with various parameters (e.g. specificity, Chromatography: A Comprehensive Reference,
precision, accuracy, detection limit, linearity, etc.) as per Springer-Verlag Berlin, 2014.
ICH guidelines. 11. R. Ong, P. Marriott, P. Morrison, P. Haglund,
Abbreviations Influence of chromatographic conditions on
API Active Pharmaceuticals Ingredients separation in comprehensive gas chromatography, J.
FID Flame Ionisation Detector Chromatogr. A, 962 (2002) 135-152
FDA Food & Drugs Administration 12. P.K. Singh, M. Pande, L.K. Singh , R.B. Tripathi,
GLC Gas Liquid Chromatography steps to be considered during method development
GC Liquid Chromatography
ICH International conference on Harmonization
and validation for analysis of residual solvents by gas
Id Internal Diameter chromatography, Int. Res J Pharm. App Sci., 3(5)
LOD Limit of Detection (2013) 74-80
LOQ Limit of Quantitation 13. T. Kupiec, Quality control Analytical Methods: Gas
m Meter Chromatography, Int. J. Pharm. Compd., 8 (4) (2004)
mm Mili meter 305-309.
MS Mass Spectrometry 14. M.S. Klee, L.M. Blumberg, Theoretical and Practical
USP United state Pharmacopeia Aspects of Fast Gas Chromatography and Method
μm Micron Translation, Journal of Chromatographic Science, 40
References:
(2002) 234-247.
1. R.L. Grob, E.F. Barry, Modern Practice of Gas
15. V. J. Barwick, Sources of uncertainty in gas
Chromatography, 4th ed., Wiley Interscience- John
chromatography and high-performance liquid
Wiley & Sons, New Jersey,2004.
chromatography, J. Chromatogr. A, 849 (1999) 13–33
2. I.A. Fowlis, Gas Chromatography-Analytical
16. M.S. Charde, A.S. Welankiwar, J. Kumar, Method
chemistry by open learning, 2nd Ed., John Wiley &
development by liquid chromatography with
Sons, New York, 1995.
validation, International Journal of Pharmaceutical
3. M. Chavan, M. Sutar, S. Deshmukh, Significance of
Chemistry, 04 (02) (2014) 57-61.
various chromatographic techniques in drug discovery
17. S. Jain, G. Kaur, V. Saini, A Review on Analytical
and development, Int. j. res. Pharm., 3(2) (2013) 282-
Method Development and Validation, Asian Journal
289.
of Biochemical and Pharmaceutical Research , 3 ( 4)
4. K. Mastovska, J. Hajslova, M. Godula, J. Krivankova,
(2014) 128-142
V. Kocourek, Fast temperature programming in
18. T. Bhagyasree, N. Injeti, A. Azhakesan, U.M.V. Rao,
routine analysis of multiple pesticide residues in food
A review on analytical method development and
matrices, J. Chromatogr. A, 907 (2001) 235 –245.
validation, International Journal of Pharmaceutical
5. S. Sood, R. Bala, N.S. Gill, Method development and
Research & Analysis, 4 (8) (2014) 444-448.
validation using HPLC technique – A review, Journal
19. A. Shrivastava, V.B. Gupta, HPLC: Isocratic or
of Drug Discovery and Therapeutics 2 (22) 2014, 18-
Gradient Elution and Assessment of Linearity in
24.
Analytical Methods, J Adv. Scient. Res, 3(2) (212)
6. P.K. Singh, M. Pande, L.K. Singh , R.B. Tripathi,
12-20.
steps to be considered during method development
20. V. Kumar, R. Bharadwaj, G.G., S. Kumar, An
and validation for analysis of residual solvents by gas
Overview on HPLC Method Development,
chromatography, Int. Res J Pharm. App Sci., 3(5)
Optimization and Validation process for drug
(2013) 74-80.
analysis, The Pharmaceutical and Chemical Journal,
7. M.S. Charde, A.S. Welankiwar, J. Kumar, Method
2(2) (2015) 30-40.
development by liquid chromatography with
21. Validation of Compendial Procedures, United State
validation, International Journal of Pharmaceutical
Pharmacopeia, USP 36 NF, 27 (2) (2010). Validation
Chemistry, 4 (1)(2014) 57-61.
of Analytical Procedures: Text and Methodology,
8. N. N. Godswill, N. E. G. Frank, M. Y. J. Edson, Y.
International Conferences on Harmonization, Draft
Emmanue, B. J. Martin, N.B. Hermine, T. M.
Revised
Kingsley, L. L.N. B. Constant, N. M. Armand,GC-

Source of support: Nil; Conflict of interest: None declared

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