Format No.

: F01/QA/001-01

STANDARD OPERATING PROCEDURE DALLAS DRUGS PVT. LTD.

BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
1.0 OBJECTIVE:
To lay down a procedure for Analytical Method Validation of Compendial or Non Compendial
methods for Active Pharmaceutical Ingredients and Excipients.

2.0 SCOPE:
This SOP is applicable to Validate Test Method which are Compendial or Non Compendial, where
Identification, Purity and Assay Test Method adopted from Scientific Literature, Technology
Transfer Document or Method Development In-house Laboratory, Compendial Method may checked
for System Suitability & System Precision, Specificity Placebo Interference, Method Precision,
Intermediate Precision, Accuracy, Robustness, Solution Stability for Active Pharmaceutical
Ingredients & Excipients in Quality Control Laboratory at Dallas Drugs Pvt. Ltd Baddi.

3.0 RESPONSIBILITY:
3.1 Officer / Executive QC.

4.0 ACCOUNTABILITY:
4.1 Head QC
4.2 Head-QA

5.0 PROCEDURE:
5.1 DEFINITIONS:
 ANALYTICAL METHOD VALIDATION:
Analytical Method Validation is the collection of documented evidence that an Analytical
Procedure is suitable for its intended use
 ACCURACY:
The Accuracy of an Analytical Procedure is the closeness of test results obtained by that
procedure to the true value. The Accuracy of an Analytical Procedure should be established
across its range.
 PRECISION:
The Precision of an Analytical Procedure is the degree of agreement among individual test
results when the procedure is applied repeatedly to multiple samplings of a homogeneous
sample.
 SPECIFICITY:
The ability to assess unequivocally the analyte in the presence of components that may be
expected to be present, such as impurities, degradation products, and matrix components.

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Format No. : F01/QA/001-01

STANDARD OPERATING PROCEDURE DALLAS DRUGS PVT. LTD.

BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
 DETECTION LIMIT:
The Detection Limit is a characteristic of limit tests. It is the lowest amount of analyte in a
sample that can be detected, but not necessarily quantitated, under the stated experimental
conditions.
 QUANTITATION LIMIT:
It is the lowest amount of analyte in a sample that can be determined with acceptable
Precision and Accuracy under the stated experimental conditions.
 LINEARITY:
The Linearity of an Analytical Procedure is its ability to elicit test results that are directly, or
by a well-defined mathematical transformation, proportional to the concentration of analyte
in samples within a given range.
 RANGE:
The Range of an Analytical Procedure is the interval between the upper and lower levels of
analyte (including these levels) that have been demonstrated to be determined with a suitable
level of Precision, Accuracy, and Linearity.
 ROBUSTNESS:
The Robustness of an Analytical Procedure is a measure of its capacity to remain unaffected
by small but deliberate variations in procedural parameters listed in the procedure
documentation and provides an indication of its suitability during normal usage.
 SYSTEM SUITABILITY :
If measurements are susceptible to variations in analytical conditions, these should be
suitably controlled, or a precautionary statement should be included in the procedure.

5.2 The most common categories for Analytical Method Validation are as follows:
5.2.1 Category-I (Assay):
Analytical Procedures for Quantitation of major components of Bulk Drug substances or
Active Ingredients (including preservatives) or Excipients.
5.2.2 Category-II (For Impurities):
5.2.3 Analytical Procedures for determination of Impurities in Bulk Drug substances. These
procedures include quantitative Assays and Limit Test.
5.2.4 Category-III:
Analytical Procedures for determination of performance characteristics (e.g., Dissolution,
Drug Release).
5.2.5 Category-IV:
Identification Test
5.3 For each category, different analytical information is needed. Elements that are normally
required for each of these categories are given in point 5.7 & 5.8.
5.4 Already established general procedures (e.g. Titrimetric Determination of Water, Bacterial
Endotoxins) should be verified to establish their suitability for use, such as their Accuracy
(and absence of possible interference) when used for a new product or Raw Material.

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Format No. : F01/QA/001-01

STANDARD OPERATING PROCEDURE DALLAS DRUGS PVT. LTD.

BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
5.5 The validity of an Analytical Procedure can be verified only by Laboratory Studies.
Therefore, documentation of the successful completion of such studies is a basic requirement
for determining whether a procedure is suitable for its intended application(s).
5.6 Current Compendial procedures are also subject to regulations that require demonstration of
suitability under actual conditions of use. Appropriate documentation should accompany any
proposal for new or revised Compendial Analytical Procedures.
5.7 ANALYTICAL METHOD VALIDATION REQUIRMENTS FOR COMPENDIAL
PRODUCTS:
Analytical Performance Category-I Category-II Category-III Category- IV
Characteristics Quantitative Limit Tests
Accuracy Yes Yes * * No

Precision Yes Yes No No

Yes
Specificity Yes Yes Yes * Yes

Detection Limit No No Yes * No

Quantitation Limit No Yes No * No

Linearity Yes Yes No * No

Range Yes Yes * * No

* May be required, depending on the nature of the Specific Test.

5.8 ANALYTICAL METHOD VALIDATION REQUIRMENTS FOR NON - COMPENDIAL PRODUCTS:

Type of Analytical Identification Testing for Impurities Assay, Dissolution
Procedure Quantitative Limit (Measurement only)
Content / Potency
Specificity + + + +
Accuracy (Recovery) - + - +
Precision - + - +
Intermediate Precision - + - +
Robustness - + - +
Forced Degradation - + - -

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STANDARD OPERATING PROCEDURE DALLAS DRUGS PVT. LTD.

BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
Type of Analytical Identification Testing for Impurities Assay, Dissolution
Procedure Quantitative Limit (Measurement only)
Solution Stability - + - Content +/ Potency

Filter Interference - + - +
Linearity - + - +
Range - + - +
Detection Limit - + + -
Quantitation Limit - + - -

5.9 ANALYTICAL PROCEDURE:

The Analytical Procedure refers to the way of performing the Analysis. It should describe in
detail the steps necessary to perform each Analytical Test. This may include but is not limited
to: the sample, the reference standard and the reagents preparations, use of the Apparatus,
Generation of the Calibration Curve, use of the Formulae for the Calculation, etc.
Types of Analytical Procedures to be validated:

The discussion of the validation of Analytical Procedures is directed to the four most
common types of Analytical Procedures:
 Identification tests;
 Quantitative tests for Impurities Content;
 Limit tests for the Control of Impurities;
 Quantitative tests of the Active Moiety in samples of Drug Substance or Drug Product or
other selected component(s) in the Drug Product.
 Analytical Procedures, such as Dissolution Testing for Drug Products
 Testing for Impurities can be either a Quantitative Test or a Limit Test for the Impurity in a
sample. Either test is intended to accurately reflect the purity characteristics of the sample.
Different validation characteristics are required for a Quantitative Test than for a Limit Test.
 Assay Procedures are intended to measure the analyte present in a given sample. The assay
represents a Quantitative measurement of the major component(s) in the Drug Substance.
For the Drug Product, similar validation characteristics also apply when assaying for the
Active or other selected component (s). The same validation characteristics may also apply to
assays associated with other Analytical Procedures (e.g., Dissolution).
5.9.1 The objective of the Analytical Procedure should be clearly understood since this will govern
the Validation Characteristics which need to be evaluated. Typical validation characteristics
which should be considered are listed below:
 Accuracy
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STANDARD OPERATING PROCEDURE DALLAS DRUGS PVT. LTD.

BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
 Precision
 Repeatability
 Intermediate Precision
 Specificity
 Detection Limit
 Quantitation Limit
 Linearity
 Range
5.9.2 The table lists those Validation Characteristics regarded as the most important for the
validation of different types of Analytical Procedures.
5.9.3 This list should be considered typical for the Analytical Procedures cited but occasional
Exceptions should be dealt with on a case-by-case basis.
5.9.4 It should be noted that Robustness is not listed in the table but should be considered at an
appropriate stage in the development of the Analytical Procedure.
5.9.5 Furthermore revalidation may be necessary in the following circumstances:
 Changes in the synthesis of the Drug Substance;
 Changes in the Analytical Procedure.
The degree of revalidation required depends on the nature of the changes. Certain other
changes may require validation as well.
5.9.6 ACCURACY:

 The accuracy of an Analytical Procedure is the closeness of test result obtained by that
procedure to the true value. The accuracy of an Analytical Procedure should be established
across its range.
 Accuracy should be assessed using a minimum of nine determinations over a minimum of
three concentration levels, covering the specified range (i.e., three concentrations and three
replicate of each concentration).
5.9.7 PRECISION:

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STANDARD OPERATING PROCEDURE DALLAS DRUGS PVT. LTD.

BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date

 The precision of an Analytical Procedure is the degree of agreement among individual test
results when the procedure is applied repeatedly to multiple samplings of a homogeneous
sample.
 The precision of an analytical procedure is usually expressed as the Standard Deviation or
Relative Standard Deviation (Coefficient of Variation) of a series of measurements.
 Precision may be a measure of either the degree of Reproducibility or of Repeatability of the
Analytical Procedure under normal operating conditions.
 In Reproducibility refers to the use of the Analytical Procedure in different laboratories, as in
a collaborative study.
 Intermediate Precision (Also known as Ruggedness) expresses within-laboratory variation, as
on different days, or with different analysts or equipment within the same laboratory.
 Repeatability refers to the use of the Analytical Procedure within a laboratory over a short
period of time using the same analyst with the same equipment.
 Repeatability should be assessed using minimum of nine determinations covering the
specified range for the procedure (i.e. three concentrations and three replicates of each
concentration or using a minimum of six determinations at 100% of the test concentration).

Inaccurate & Accurate but

Inaccurate but imprecise imprecise
precise
Accurate & Precise which is
requirement of the Method

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STANDARD OPERATING PROCEDURE DALLAS DRUGS PVT. LTD.

BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
[

5.9.8 SPECIFICITY:
Specificity is defined as the ability to assess unequivocally the analyte in the presence of
components that may be expected to be presence, such as Impurities, Degradation Products
and Matrix components. Lack of specificity of an individual analytical procedure may be
compensated by other supporting analytical procedure.
 International Authorities have preferred the term “Selectivity”, reserving “Specificity” for
those procedure that are completely selective] For the tests discussed below, the above
definition has the following implications:
 Identification Tests: ensures the identity of the analyte.
 Purity Tests:
Ensure that all the Analytical Procedures, performed allow an accurate statement of the
content of Impurities of an analyte (e.g. related substances test, Heavy Metals Limit and
Organic Volatile Impurities).

 Assay:
 Provide an exact result, which allows an accurate statement on the content or potency of the
analyte in a sample.
 When Chromatographic Procedures are used, representative Chromatograms should be
presented to demonstrate the degree of selectivity, and peaks should be appropriately labeled.
Peak Purity Tests (e.g. using Diode Array or Mass Spectrometry) may be useful to show that
the analyte Chromatographic Peak is not attributable to more than one component.

5.9.9 LINEARITY:

 The Linearity of an Analytical Procedure is its ability to elicit test results that are directly
proportional to the concentration of analyte in samples within a give range. Thus,

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STANDARD OPERATING PROCEDURE DALLAS DRUGS PVT. LTD.

BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
“Linearity” refers to the linearity of the relationship of concentration and assay
measurement.
In some cases, to attain linearity, the concentration and / or the measurement may be transformed.
(Note that the weighing factors used in the regression analysis may change when a
transformation is applied).
 Possible transformations may include Log, Square Root, or Reciprocal, although other
transformation is acceptable. If Linearity is not attainable, a Nonlinear Model may be used.
The goal is to have a model, whether Linear or Nonlinear, that describes closely the
concentration-response relationship.
 For the establishment of Linearity, a minimum of Five Concentrations normally be used.
Minimum Specified Ranges should be considered:

5.9.10 RANGE:
 The range of an Analytical Procedure is the interval between the upper and lower levels of
analyte (including these levels) that have been demonstrated to be determined with a suitable
level of Precision, Accuracy, and Linearity using the procedure as written.
 The range is normally expressed in the same units as test results (e.g. Percent, Parts per
Million) obtained by the Analytical Procedure.

5.9.11 DETECTION LIMIT:

 The Detection Limit is a characteristic of Limit Tests. It is the lowest amount of analyte in a
sample that can be detected, but not necessarily quantitated, under the stated experimental
conditions. Thus, limit test merely substantiate that the amount of analyte is above or below a
certain level.
 The detection limit is usually expressed as the concentration of analyte (e.g. percentage, part
per billion) in the sample.
 In the case of Instrumental Analytical Procedure that exhibit background Noise is to compare
measurement single from sample with known Low Concentrations of analyte with those of
Blank Samples.
 The minimum concentration at which the analyte can reliably be deducted is established.
Typically acceptable signals-to-noise ratios are 2:1 or 3:1.
 Other approaches curve and the Standered Deviation of responses. Whatever method is used,
the detection limit should be subsequently validated by the analysis of a suitable number of
samples known to be near, or prepared at, the Detection Limit.

5.9.12 QUANTITATION LIMIT:

 The Quantitation Limit is a characteristic of Quantitative Assay for low levels of compounds
in sample matrices, such as impurities in bulk drug substances.
 It is the lowest amount of analyte in a sample that can be determined with acceptable
Precision and Accuracy under the stated experimental conditions.

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BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
 The Quantitation Limit is expressed as the concentration of analyte (e.g. percentage, part per
billion) in the sample.
 In the case of instrumental Analytical Procedure that exhibit background noise, the ICH
documents describe a common approach, which is to compare measured signal from sample
with known low concentrations of analyte with those of blank samples.
 The minimum concentration at which the analyte can reliably be quantified is established. A
typically acceptable signal-to-noise ratio shall be 10:1.
 Other approaches depend on the determination of the slope of the calibration curve and the
Standard Deviation of responses. Whatever approach is used, the Quantitation Limit should
be subsequently validated by the analysis of a suitable number of samples known to be near,
or prepared at the Quantitation Limit.
5.9.13 SAMPLE SOLUTION STABILITY:
 Solution Stability of the drug substance or drug product after preparation according to the test
method should be evaluated according to the test method. Most laboratory utilize auto
sampler with overnight runs and the sample shall be in solution for hours in the laboratory
environment before the test procedure is completed.
 This is of concern especially for drug that can undergo degradation by hydrolysis, Photo
Analysis or Adhesion to glassware.
 Recommendations:
 Data to support the sample solution under normal laboratory condition for the duration of the
test procedure e.g. twenty-four hours should be generated.
 In exceptional cases where multiple days are needed for sample preparation or solution
storage, an appropriate stability time should be selected.

5.9.14 SPECIFICITY / SELECTIVITY:

 The analyte should have no interference from other extraneous components and be well
resolved from them. A representative HPLC or profile resolved should be generated and
submitted to show that the extraneous peak either by addition of known compound or
samples from stress testing are baseline resolved from the parent analyte.
 For the drug substance or raw material , the related substance to consider are process impurity
(which include isomeric impurities) for the synthesis process, residual pesticides, solvent and
other extraneous components from extracts of natural origin.
 For the drug product, the related substances may be impurities present in the active drug,
degradation product, interaction of the active drug with excipients, extraneous components
e.g. residual solvent from the excipients or manufacturing process, leachables or extractable
from the container and closure system or from the manufacturing process.
 Representative HPLC are recommended for stressed and non stressed samples that include
test method for impurity test method, the HPLC should indicate the presence of impurities at
the level of chromatogram should indicate the presence of impurities at the level of Detection
/ Quantitation claimed. The chromatograms should be legible, labeled, and the time or time
scale and attenuation should be indicated.
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BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
Points to note are as follows:
 The parent peak may be expanded e.g. by increasing the concentration. Attenuation change,
so that extraneous peaks can be observed at a reasonable size to evaluate Stability indicating
capability.
 The baseline should be on scale as off-scale baseline (observed as a flat straight line can hide
minor peaks.) can hide minor peak.
 Peak purity can be determined by PDA detector.
 Stress Analysis should be acidic, base hydrolysis, Temperature, Photo Analysis and
Oxidation.
 Non- Stress Analysis should be as per Standard Testing Procedure.

5.9.15 IDENTIFICATION: to ensure the identity of an Analyte

5.9.16 ASSAY:
when impurity are available spike the drug substance/ drugs product with
appropriate level of Impurity / Excipients and demonstrate he assay not affecting there And
when impurity are not available inject the test sample, prepared degradated / expired using to
analysis and compare the result with our standard method

5.9.17 IMPURITY PROFILE:

When impurity available spike drug substance / drug product with appropriate level of
impurity and demonstrate separation this impurity individually and form other component of
complex. In case of Impurity not available, subject the test sample, prepared degradated /
expire sample to analyze and compare the result with respective impurity profile.
Recommendation:
 Representative HPLC should be submitted for stressed and no stressed sample that include
impurities test method, preservative(s), etc. with the related placebo sample. Representative
HPLC to show selectivity by the addition of know extraneous compound.

5.9.18 SYSTEM SUITABILITY SPECIFICATION AND TESTS:

If measurements are susceptible to variations in analytical conditions, these should be
suitably controlled, or a precautionary statement should be included in the procedure. One
consequence of the evaluation of robustness and ruggedness should be that a series of system
suitability parameters is established to ensure that the validation of the analytical procedure is
maintained whenever used.
 Typical variations are the stability of analytical solutions, different equipment, and different
analysts.
 In the case of liquid chromatography, typical variations are the pH of the mobile phase, the
mobile phase composition, different lots or suppliers of columns, the temperature, and the
flow rate.
 In the case of Gas Chromatography, typical variations are different lots or suppliers of
columns, the temperature, and the flow rate.
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BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
 Capacity Factor should be k’ NMT 2
K’ = tr-to / to
Where,
k’: Capacity factor,
tr : Retentions time of the analyte,
to : Elution time of the volume or non-retained components.

 Precision / Injection Repeatability (RSD) NMT 1 % of Five Injections

 Resolution (Rs) : Rs = ( tr2-tr1) / (1/2)( tw1-tw2)
Where,
Rs = is a measure of the how well two peak are separated.

 Tailing Factor NMT 2 .0

T = Wx / 2f
 Theoretical Plate Number (N) NLT 2000
N= 16 (tr / tw) 2
OR new developed analytical method for new product then following parameter are to be
consider in Analytical Method Validation.
 Precision
 Linearity
 Accuracy
 Range / Recovery
 Specificity
 LOD
 LOQ
 Robustness

For Officials analytical method following parameter are to consider only in Analytical
Method Validation.
 Precision
 Linearity
 Accuracy / Recovery

5.9.19 CHANGE in brand name of product only and generic active ingredient are same and only
change in strength then consider the validation of same product.
5.9.20 OBSERVATION:
To be clear the criticality in the method.

5.9.21 COMMENTS AND CONCLUSION:

HPLC Method for Drug Product:

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BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
 Methods should not be validate as a onetime situation, but methods should be validated and
designed by the developer or user to ensure ruggedness or robustness throughout the life of
the method.
 The variation due to the drug product manufacturing process, the laboratory sample
preparation procedure and the instrument performance contribute to the Accuracy of the data
obtained from the analysis.
5.9.22 With proper validation and tight Chromatographic Performance (System Suitability) criteria,
an improvement in the reliability of the data can be obtained.

5.10 VALIDATION ELEMENTS AND ACCEPTANCE CRITERIA (CATEGORY-I):

S. No. Validation Elements Acceptance Criteria
1. Precision  The RSD of the determinations (injections) of each
analyte should be NMT 2.0%
2. Accuracy  The average Recovery for each analyte must be NLT
98% and NMT 102% for triplicate determinations at
analyte concentration of 80%, 100% & 120% of target
concentration.
3. Specificity  No peak interference in the Placebo Injection at the
retention time of target analyte.
 The target analyte peak is resolved from adjacent
peak(s).
 The target analyte peak is pure by PDA analysis under
Forced Degradation conditions
4. Method Linearity  These acceptance criteria must be met for a 5 point
concentration range of at least 80% to 120% of the
target concentration.
 The Correlation Coefficient (r) is NLT 0.995
 The percentage as of Y intercept is NLT -5% & NMT
10%
5. Range  The Precision, Accuracy and Linearity Criteria must be
met at least 80% and about 120% of sample
concentration.
 The range is larger, report the larger range over which
the acceptance criteria are met.

6. Ruggedness  The RSD of the spiked sample preparations from a

(Intermediate Precision) second analyst, on a second instrument, and on a
different day using different column must be NMT
2.0%.
 The RSD of the spiked sample preparations from both

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BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
S. No. Validation Elements Acceptance Criteria
analyte and analysts two must be NMT 5.0%

7. Filter Interference  The assay of the Filtered Sample must be NLT 98.0% &
(Where Applicable) NMT 102.0% relative to the same sample prepared by
Centrifugation
8. Solution Stability  The Assay of the sample preparation must not change by
(ambient or refrigerated more than 2% in a specified time period
temperature)  The Assay of the Working Standard must not change by
more than 2% in a specified time period
9. Robustness  System Suitability criteria are met for the following
Method Variations:
 Variation of Organic Component in the Mobile Phase±
5% (relative)
 Variation of Ion-Paring concentration of ±10%, when
applicable
 Variation of Mobile Phase pH of ±01. pH units, when
applicable
 variation of Flow Rate about±10%
 Variation of Wavelength±2nm
 Variation of Column Temperature about ±5oC (where
applicable)

5.11 VALIDATION ELEMENTS AND ACCEPTANCE CRITERIA (CATEGORY-II):

S. No. Validation Elements Acceptance Criteria
1. Precision  RSD is NMT 10.0%
2. Accuracy  Recovery for Target Analyte is between 90% and 110%
for spiked Placebo samples for method range
3. Linearity  The Correlation Coefficient (r) is NLT 0.99 for the
Method Range
 The 95% confidence interval of the intercept includes the
origin. If not, the intercept is NMT 100± 10% of the
response of the Standard Concentration (at the
Specification Level)
4. Range  The concentration at which the Precision, Accuracy and
Linearity Criteria are met. This Range should be from
the LOQ to 150% of the Specification Level
5. Quantitation Limit  The Concentration at which the S/N ratio is about 10. the
Quantitation Limit should be NMT the reporting
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BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
S. No. Validation Elements Acceptance Criteria
threshold defined in ICH Q3B
6. Detection Limit  The concentration at which the S/N ratio is about 3.
 The Detection Limit should be NMT half of the reporting
threshold defined in ICH Q3B
7. Specificity  No peak interference in the Placebo Injection at the
retention time of Target Analyte(s).
 The known Impurity Peak(s) are resolved from each
other and from the Active Substance Peak(s).
 The target Analyte peak(s) are pure by PDA analysis
under Forced Degradation Conditions
8. Ruggedness  The Precision and Accuracy acceptance criteria for a
second analyst must be met for a standard spiked
Placebo Solution on a separate instrument using a
different Column with sample solution prepared on a
different day at the specification limit concentration
level
 The combined RSD(s) of the Analyte(s) for both
Analysts must be NMT 15.0%
9. Filter Interference  The peak area of each know impurity peak must be
(Where Applicable) within 100±10% of Centrifuged Solution
10. Robustness  System Suitability Criteria are met for the following
Method Variations:
 Variation of Organic Component in the Mobile Phase±
5% (relative)
 Variation of Ion-paring concentration of ±10%, where
applicable
 Variation of mobile phase pH ±01. pH units, when
applicable
 variation of flow rate about±10%
 Variation of wavelength±2nm
 Variation of column temperature about±5oC (where
applicable)
11. Solution Stability The Assay of the Standard and sample solutions at room
temperature (or refrigerated temperature) must not change by
more than 5% in a specified time period at least as long as
the time required to perform a typical analysis run
(maximum analysis time from Sample Preparation should be
defined in the Test Method).

Prepared by Reviewed by Approved by Authorized by

Sign/Date

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Format No. : F01/QA/001-01

STANDARD OPERATING PROCEDURE DALLAS DRUGS PVT. LTD.

BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
5.12 Record shall be maintained in Validation Protocol and Validation Report As per respective
SOP.

6.0 REFERENCES:
6.1 ICH Harmonized Tripartite Guideline
6.2 USP

7.0 ANNEXURE:
Not applicable

8.0 FORMATS:
Not applicable

9.0 ABBREVIATIONS:
SOP Standard Operating Procedure
No. Number
QA Quality Assurance
QC Quality Control
ICH International Conference on Harmonization of Technical Requirements for
Registration of Pharmaceuticals for Human Use
LOD Limit of Detection
LOQ Limit of Quantification
USP United State of Pharmacopoeia
RSD Relative standard deviation
HPLC High Performance Liquid Chromatography

10.0 DISTRIBUTION LIST:

This SOP shall be distributed all below mentioned departments in the manufacturing facility of
Dallas Drugs Pvt. Ltd.
Sr. No. Department
1. Quality Assurance
2. Quality Control

11.0 CHANGE HISTORY:*

Revision Number Change Control Number Reason For Revision

00 Nil New SOP
01 CC/22/011 Typo error, Formating
Prepared by Reviewed by Approved by Authorized by

Sign/Date

Page 15 of 16
Format No. : F01/QA/001-01

STANDARD OPERATING PROCEDURE DALLAS DRUGS PVT. LTD.

BADDI
ANALYTICAL METHOD VALIDATION OF COMPENDIAL OR NON
Title COMPENDIAL METHODS FOR ACTIVE PHARMACEUTICAL INGREDIENTS
AND EXCIPIENTS
SOP Number QC/003-01 Supersedes 00 Effective Date
Department Quality Control Review Date
*Current revision shall be mentioned in reverse manner.

End of the document

Prepared by Reviewed by Approved by Authorized by

Sign/Date

Page 16 of 16