Published on USP Medicines Compendium (https://mc.usp.

org)

Domperidone Tablets

Proposed For Comment Version 0.2

DEFINITION
Domperidone Tablets contain an amount of Domperidone Maleate equivalent to NLT 95.0% and NMT 105.0% of the labeled amount of
domperidone (C22H24ClN5O2).

Performance-Based Monograph
(Contains tests, procedures, and acceptance criteria for the material under test. It also includes the criteria-based procedures to
demonstrate that an Acceptable Procedure is equivalent to the Reference Procedures.)

IDENTIFICATION
• A. The response for domperidone from the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

ASSAY
• PROCEDURE
Standard solution: USP Domperidone Maleate RS in an appropriate diluent
Sample solution: Dissolve a portion of Tablets in an appropriate diluent to obtain a concentration approximately the same as that of
the Standard solution.
Analytical system: Use a procedure validated as described in MC general chapter Assessing Validation Parameters for Reference
and Acceptable Procedures <10>.
System performance requirements
Precision: Meets the requirements for 98.0%–102.0%
Accuracy: Meets the requirements for 98.0%–102.0%
Specificity: Meets the requirements
Range: Meets the requirements
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of domperidone (C22H24ClN5O2) in the Sample solution:

Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100

rU = response from the Sample solution

rS = response from the Standard solution
CS = concentration of USP Domperidone Maleate RS in the Standard solution
CU = nominal concentration of domperidone in the Sample solution
Mr1 = molecular weight of domperidone, 425.91
Mr2 = molecular weight of domperidone maleate, 541.98
Acceptance criteria: 95.0%–105.0%

PERFORMANCE TESTS
• DISSOLUTION <711>
Medium, Apparatus, Time, and Acceptance criteria: See MC general chapter Assessing Drug Product Performance <12>.
Standard solution: USP Domperidone Maleate RS in an appropriate diluent
Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, and dilute with an
appropriate diluent to obtain a concentration approximately the same as that of the Standard solution.
Instrumental conditions: Proceed as directed in the Assay or in an alternatively validated procedure.
• UNIFORMITY OF DOSAGE UNITS <905>: Meets the requirements

IMPURITIES
• ELEMENTAL IMPURITIES <232>: Proceed as directed in the chapter.
• RESIDUAL SOLVENTS <467>: Proceed as directed in the chapter.
• ORGANIC IMPURITIES
Standard solution: USP Domperidone Maleate RS and all appropriate USP Impurity RSs, at concentrations corresponding to the
Acceptance criteria of the impurity, in an appropriate diluent
Sample solution: Dissolve a portion of Tablets in an appropriate diluent to obtain an appropriate nominal concentration of
domperidone.
Analytical system: Use a procedure validated as described in MC general chapter Assessing Validation Parameters for Reference
and Acceptable Procedures <10>.
System performance requirements
Precision: Meets the requirements
Accuracy: Meets the requirements
Ruggedness: Meets the requirements
Specificity: Meets the requirements
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of each impurity in the Sample solution:

Result = (rU/rS) × (CS/CU) × 100

rU = response of each impurity from the Sample solution

rS = response of each USP Impurity RS from the Standard solution. [NOTE—If no USP Impurity RSs are available, use the response of
domperidone.]
CS = concentration of standard material in the Standard solution
CU = nominal concentration of domperidone in the Sample solution
Acceptance criteria
Any individual impurity: NMT 0.2%

ADDITIONAL REQUIREMENTS
• REFERENCE STANDARDS <11>
USP Domperidone Maleate RS
USP Domperidone Impurity A RS
5-Chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzimidazol-2-one.
USP Domperidone Impurity B RS
4-(5-Chloro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-formylpiperidine.
USP Domperidone Impurity C RS
cis-4-(5-Chloro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-[3-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)propyl]piperidine 1-oxide.
USP Domperidone Impurity D RS
5-Chloro-3-[3-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)propyl]-1-{1-[3-(2-oxo-2,3-dihydro-1H
-benzimidazol-1-yl)propyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one.
USP Domperidone Impurity E RS
1-{3-[4-(5-Chloro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]propyl}-3-[3-(2-oxo-2,3-dihydro-1H
-benzimidazol-1-yl)propyl]-1,3-dihydro-2H-benzimidazol-2-one.
USP Domperidone Impurity F RS
1,3-Bis{3-[4-(5-chloro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]propyl}-1,3-dihydro-2H-benzimidazol-2-one.
USP Droperidol RS
1-{1-[3-(p-Fluorobenzoyl)propyl]-1,2,3,6-tetrahydro-4-pyridyl}-2-benzimidazolinone.

REFERENCE PROCEDURES
(This section provides detailed descriptions of procedures that may be used for the evaluation of the material under test. These
procedures have been validated, and the summary of the data is available on the MC website.)

ASSAY
• PROCEDURE
 Solution A: 0.05% Trifluoroacetic acid in water
Solution B: 0.05% Trifluoroacetic acid in methanol and ethanol (19:1)
Diluent: 0.05% Trifluoroacetic acid in water and methanol (1:1)
Mobile phase: See Table 1.

Table 1

Time Solution A Solution B

(min) (%) (%)

0 70 30

5 65 35

20 54 46

26 36 64

30 20 80

30.5 70 30

40 70 30

System suitability solution: 5 µg/mL each of USP Domperidone Maleate RS and USP Droperidol RS in Diluent
Standard solution: 0.1 mg/mL of USP Domperidone Maleate RS in Diluent
Sample solution: Weigh and finely powder an adequate number of Tablets, and dissolve a portion in Diluent. Sonicate, centrifuge,
and filter to obtain a final domperidone maleate concentration of 0.1 mg/mL.
Chromatographic system
(See Chromatography <621>, System Suitability.)
Mode: LC
Detector: PDA (scan 200–400 nm). [NOTE—Calculations should be based on the chromatograms collected at 285 nm.]
[NOTE—To confirm the absence of co-eluting known and unknown impurity peaks, substitute the Reference Procedures, Impurities,
Detector.]
Column: 4.6-mm × 25-cm; 5-µm packing L1 (similar to Waters Symmetry C18)
Temperatures
Column oven: 35°
Autosampler: 10°
Flow rate: 1 mL/min
Injection volume: 20 µL
System suitability
Samples: System suitability solution and Standard solution
Suitability requirements
Resolution: NLT 2.0 between droperidol and domperidone peaks, System suitability solution
Relative standard deviation: NMT 1.0% for the domperidone peak, Standard solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of domperidone (C22H24ClN5O2) in the portion of Tablets taken:

Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100

rU = peak response of domperidone from the Sample solution

rS = peak response of domperidone from the Standard solution
CS = concentration of USP Domperidone Maleate RS in the Standard solution. [NOTE—The potency of the Reference Material is
included in this term.]
CU = concentration of domperidone in the Sample solution
Mr1 = molecular weight of domperidone, 425.91
Mr2 = molecular weight of domperidone maleate, 541.98

IMPURITIES
• ORGANIC IMPURITIES
 Solution A, Solution B, Diluent, Mobile phase, and Chromatographic system: Proceed as directed in Reference Procedures,
Assay.
System suitability solution: Proceed as directed for the Standard solution in Reference Procedures, Assay.
Standard solution: 0.5 µg/mL each of USP Domperidone Maleate RS, USP Domperidone Impurity A RS, USP Domperidone Impurity B
RS, USP Domperidone Impurity C RS, USP Domperidone Impurity D RS, USP Domperidone Impurity E RS, USP Domperidone Impurity F
RS, and USP Droperidol RS in Diluent
Sample solution: Weigh and finely powder an adequate number of Tablets, and dissolve a portion in Diluent. Sonicate, centrifuge,
and filter to obtain a final domperidone maleate concentration of 0.5 mg/mL.
Detector: PDA and MS
PDA wavelengths: 200–400 nm. [NOTE—Where Reference Standards are available a peak maximum wavelength should be chosen
for calculations, otherwise, calculations should be made at an isobestic point of the drug substance and impurity spectra or at 285
nm if an isobestic point is not available.]
MS source: ES scan (+ and –)
MS conditions
Source temperature: 120°
Desolvation temperature: 450°
System suitability
Samples: System suitability solution and Standard solution
Suitability requirements
Resolution 1: NLT 2.0 between droperidol and domperidone peaks, Standard solution
Resolution 2: NLT 1.5 between impurity D and impurity E peaks, Standard solution
Relative standard deviation: NMT 1.0% for the domperidone peak, System suitability solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken. [NOTE—Where an impurity other than those included in
the Standard solution is found in the Sample solution, the peak response and concentration of domperidone in the Standard solution
are used for the calculation.]

Result = (rU/rS) × (CS/CU) × 100

rU = peak response of each impurity from the Sample solution

rS = peak response of each impurity from the Standard solution
CS = concentration of each impurity in the Standard solution. [NOTE—The potency of the Reference Material is included in this
term.]
CU = concentration of domperidone in the Sample solution

Source URL (modified on 2014/06/30 - 12:00am): https://mc.usp.org/monographs/domperidone-tablets-0-2