Printed on: Wed Feb 08 2023, 11:48:34 PM(EST) Status: Currently Official on 09-Feb-2023 DocId: GUID-BF7F4422-A018-49C0-B9EB-65773E07DDF7_1_en-US

Printed by: Dang Van Vu Official Date: Official as of 01-Dec-2017 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: 0h0mi DOI: https://doi.org/10.31003/USPNF_M70160_01_01
1

Suitability requirements
Promethazine Hydrochloride Oral Resolution: NLT 5.0 between promethazine and
Solution promethazine related compound B peaks, System
suitability solution
DEFINITION Tailing factor: NMT 2.0, Standard solution
Promethazine Hydrochloride Oral Solution contains NLT Relative standard deviation: NMT 1.0%, Standard
90.0% and NMT 110.0% of the labeled amount of solution
promethazine hydrochloride (C17H20N2S · HCl). Analysis
[NOTE—Throughout the following procedures, protect the Samples: Standard solution and Sample solution
samples, the Reference Standards, and the solutions Calculate the percentage of the labeled amount of
containing them, by conducting the procedures without promethazine hydrochloride (C17H20N2S · HCl) in the
delay, under subdued light or using low-actinic portion of Oral Solution taken:
glassware.]
Result = (rU/rS) × (CS/CU) × 100
IDENTIFICATION
• A. The retention time of the major peak of the Sample rU = peak response from the Sample solution
solution corresponds to that of the Standard solution, as rS = peak response from the Standard solution
obtained in the Assay.
CS = concentration of USP Promethazine
• B. The UV spectrum of the major peak of the Sample
Hydrochloride RS in the Standard solution
solution corresponds to that of the Standard solution, as
(mg/mL)
obtained in the Assay.
CU = nominal concentration of promethazine
ASSAY hydrochloride in the Sample solution (mg/mL)

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• PROCEDURE
Buffer: 3.7 g/L of ammonium acetate in water Acceptance criteria: 90.0%–110.0%
Solution A: Acetonitrile and Buffer (30:70) IMPURITIES
Solution B: Acetonitrile • ORGANIC IMPURITIES
Mobile phase: See Table 1. ci Buffer, Solution A, Solution B, Mobile phase, Diluent, and
Chromatographic system: Proceed as directed in the
Table 1
Assay.
Time Solution A Solution B Standard solution: 1.0 µg/mL each of USP Promethazine
(min) (%) (%)
Hydrochloride RS and USP Promethazine Related
0 100 0 Compound B RS in Diluent
ffi
Sample solution: Nominally 500 µg/mL of promethazine
10 60 40
hydrochloride from a volume of Oral Solution in Diluent.
18 60 40 Centrifuge for 10 min and use the supernatant.
[NOTE—Sonication may be used in the preparation of the
18.1 100 0
Standard solution and the Sample solution.]
25 100 0 System suitability
O

Sample: Standard solution

Diluent: 0.1% triethylamine in methanol [NOTE—See Table 2 for relative retention times.]
System suitability solution: 1.0 µg/mL each of USP Suitability requirements
Promethazine Hydrochloride RS and USP Promethazine Resolution: NLT 5.0 between promethazine and
Related Compound B RS in Diluent promethazine related compound B peaks
Standard solution: 0.05 mg/mL of USP Promethazine Relative standard deviation: NMT 5.0% for
Hydrochloride RS in Diluent promethazine
Sample solution: Nominally 0.05 mg/mL of promethazine Analysis
hydrochloride from a volume of Oral Solution in Diluent. Samples: Standard solution and Sample solution
Centrifuge for 10 min and use the supernatant. Calculate the percentage of each degradation product in
[NOTE—Sonication may be used in the preparation of the the portion of Oral Solution taken:
System suitability solution, Standard solution, and
Sample solution.] Result = (rU/rS) × (CS/CU) × (1/F) × 100
Chromatographic system
rU = peak response of each degradation product
(See Chromatography á621ñ, System Suitability.)
from the Sample solution
Mode: LC
rS = peak response of promethazine from the Standard
Detector: UV 254 nm. For Identification test B, use a diode
solution
array detector in the range of 200–400 nm.
CS = concentration of USP Promethazine
Column: 4.6-mm × 15-cm; 5-µm packing L1
Hydrochloride RS in the Standard solution
Temperatures
(µg/mL)
Autosampler: 4°
CU = nominal concentration of promethazine
Column: 30°
hydrochloride in the Sample solution (µg/mL)
Flow rate: 1.4 mL/min
F = relative response factor (see Table 2)
Injection volume: 15 µL
System suitability Acceptance criteria: See Table 2. Disregard peaks less than
Samples: System suitability solution and Standard solution 0.05%.
[NOTE—The relative retention times for promethazine
and promethazine related compound B are 1.0 and
1.3, respectively.]

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Printed on: Wed Feb 08 2023, 11:48:34 PM(EST) Status: Currently Official on 09-Feb-2023 DocId: GUID-BF7F4422-A018-49C0-B9EB-65773E07DDF7_1_en-US
Printed by: Dang Van Vu Official Date: Official as of 01-Dec-2017 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: 0h0mi DOI: https://doi.org/10.31003/USPNF_M70160_01_01
2

Table 2 a N,N-Dimethyl-1-(10H-phenothiazin-10-yl)propan-2-amine sulfoxide.

b N-Methyl-1-(10H-phenothiazin-10-yl)propan-2-amine.
Relative Relative Acceptance
c This is a process impurity which is controlled in the drug substance and is
Retention Response Criteria,
Name Time Factor NMT (%) included in the table for identification only.
d 10H-Phenothiazine.
Promethazine
sulfoxidea 0.3 0.26 1.0
ADDITIONAL REQUIREMENTS
Desmethyl promethazine b
0.6 1.0 0.2 • PACKAGING AND STORAGE: Preserve in tight, light-resistant
Promethazine 1.0 — —
containers.
• USP REFERENCE STANDARDS á11ñ
Promethazine related com-
— — USP Promethazine Hydrochloride RS
pound Bc 1.3 USP Promethazine Related Compound B RS
Phenothiazined 1.5 2.2 0.2 Isopromethazine hydrochloride;
N,N-Dimethyl-2-(10H-phenothiazin-10-yl)propan-1-
Any individual amine hydrochloride.
unspecified —
degradation product 1.0 0.2 C17H20N2S · HCl 320.88

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