Prochlorperazine Maleate Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision, please click https://www.uspnf.com/rb-prochlorperazine-maleate-tabs-20220930. 

1 DEFINITION 

Prochlorperazine Maleate Tablets contain an amount of Prochlorperazine Maleate equivalent to NLT 95.0% and NMT 105.0% of the labeled amount of prochlorperazine (C₂₀H₂₄ClN₃S). 

[Note—Throughout the following procedures, protect the samples, Reference Standards, and solutions from light, and conduct the procedures without delay.] 

2 IDENTIFICATION 

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 

3 ASSAY 

Procedure 

Ion-pairing solution: Dissolve 4.33 g of sodium 1-octanesulfonate in 500 mL of water. Add 4.0 mL of glacial acetic acid, and dilute with water to 1 L. 

Mobile phase: Acetonitrile, methanol, and Ion-pairing solution (40:15:45) 

Standard solution: 0.2 mg/mL of USP Prochlorperazine Maleate RS in Mobile phase 

Sample solution: Nominally equivalent to 0.12 mg/mL of prochlorperazine in Mobile phase prepared as follows. Transfer an equivalent to about 12 mg of prochlorperazine from finely powdered Tablets (NLT 20), to a 100-mL volumetric flask. Add 60 mL of Mobile phase, sonicate for 3 min, and shake by mechanical means for 30 min. Dilute with Mobile phase to volume, and filter, discarding the  first 10 mL of  filtrate. Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm. For Identification B, use a diode array detector in the range of 210–400 nm. 

Column: 3.9-mm × 30-cm; 10 µm packing L1 

Flow rate: 2 mL/min 

Injection volume: 10 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.0 

Relative standard deviation: NMT 1.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of prochlorperazine (C₂₀H₂₄ClN₃S) in the portion of Tablets taken: 

Result = (r_U/r_S) × (C_S/C_U) × (M_R1/M_R2) × (1/F) × 100 

r_U = peak response of prochlorperazine from the the Sample solution 

r_S = peak response of prochlorperazine from the the Standard solution

C_S = concentration of USP Prochlorperazine Maleate RS in the Standard solution (mg/mL) 

C_U = nominal concentration of prochlorperazine in the Sample solution (mg/mL) 

M_R1 = molecular weight of prochlorperazine, 373.94

M_R2 = molecular weight of prochlorperazine maleate, 606.09  

Acceptance criteria: 95.0%–105.0% 

4 PERFORMANCE TESTS 

Change to read: 

Dissolution 〈711〉 

Test 1   filtrate 

Medium: 0.1 N hydrochloric acid; 500 mL 

Apparatus 2: 75 rpm 

Time: 60 min 

Standard solution: USP Prochlorperazine Maleate RS at a known concentration in Medium 

Sample solution: Pass a portion of the solution under test through a suitable filter, and dilute with Medium, if necessary, to a concentration that is similar to that of the Standard solution. 

Instrumental conditions 

Mode: UV 

Analytical wavelength: 254 nm 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of prochlorperazine (C₂₀H₂₄ClN₃S) dissolved: 

Result = (A_U/A_S) × C_S × V × D x (M_R1/M_R2) × (1/L) × 100 

A_U = absorbance of the Sample solution 

A_S = absorbance of the Standard solution

C_S = concentration of USP Prochlorperazine Maleate RS in the Standard solution (mg/mL)  

V = volume of Medium, 500 mL 

D = dilution factor for Sample solution, if needed

M_R1 = molecular weight of prochlorperazine, 373.94

M_R2 = molecular weight of prochlorperazine maleate, 606.09  L = label claim (mg/Tablet) 

Tolerances: NLT 75% (Q) of the labeled amount of prochlorperazine (C₂₀H₂₄ClN₃S) is dissolved. 

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2. 

Medium: 0.1 N hydrochloric acid; 500 mL 

Apparatus 2: 50 rpm 

Time: 30 min 

Standard stock solution: 0.275 mg/mL of USP Prochlorperazine Maleate RS prepared as follows. Transfer a suitable amount of USP Prochlorperazine Maleate RS to a suitable volumetric flask. Add 10% of the flask volume of acetonitrile and 60% of the flask volume of Medium and sonicate to dissolve. Dilute with Medium to volume. 

Standard solution: (L/500) mg/mL of prochlorperazine prepared as follows, where L is the label claim in mg/Tablet. Dilute the Standard stock solution with Medium to obtain a solution with a nal concentration of 0.0165 mg/mL of USP Prochlorperazine Maleate RS for Tablets labeled to contain 5 mg and 0.033 mg/mL of USP Prochlorperazine Maleate RS for Tablets labeled to contain 10 mg. 

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size, discarding the  first 5 mL of filtrate. Instrumental conditions 

Mode: UV 

Analytical wavelength: 254 nm 

Cell path length: 0.5 cm 

Blank: Medium 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of prochlorperazine (C₂₀H₂₄ClN₃S) dissolved

Result = (A_U/A_S) × C_S × V × (M_R1/M_R2) × (1/L) × 100 

A_U = absorbance of the Sample solution 

A_S = absorbance of the Standard solution

C_S = concentration of USP Prochlorperazine Maleate RS in the Standard solution (mg/mL)  

V = volume of Medium, 500 mL 

M_R1 = molecular weight of prochlorperazine, 373.94

M_R2 = molecular weight of prochlorperazine maleate, 606.09  

L = label claim (mg/Tablet) 

Tolerances: NLT 80% (Q) of the labeled amount of prochlorperazine (C₂₀H₂₄ClN₃S) is dissolved.   filtrate 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 IMPURITIES

Organic Impurities 

Buffer solution: 1.36 g/L of sodium acetate trihydrate in water (0.01 M). Add 2.0 mL of triethylamine and 6.0 mL of glacial acetic acid per liter of solution. 

Solution A: Buffer solution 

Solution B: Acetonitrile 

Mobile phase: See Table 1. Return to original conditions, and re-equilibrate the system for about 10 min. 

Table 1 

Diluent: Acetonitrile and water (40:60) 

Impurity stock solution: 0.16 mg/mL of USP Prochlorperazine Related Compound A RS in Diluent 

Standard stock solution: 0.16 mg/mL of USP Prochlorperazine Maleate RS in Diluent 

System suitability solution: 1.6 µg/mL of USP Prochlorperazine Maleate RS and 1.6 µg/mL of USP Prochlorperazine Related Compound A RS in Diluent from the Standard stock solution and the Impurity stock solution, respectively 

Standard solution: 0.0064 mg/mL of USP Prochlorperazine Maleate RS in Diluent from the Standard stock solution Sample solution: Nominally equivalent to 0.4 mg/mL of prochlorperazine in Diluent, prepared as follows. Transfer 20 Tablets to a suitable volumetric flask, using a 250-mL volumetric flask for 5-mg Tablets and a 500-mL volumetric flask for 10-mg Tablets. Add Diluent to about 80% of the nal flask volume, sonicate with occasional swirling for 10 min or shake by mechanical means for 20 min, and dilute with Diluent to volume. Centrifuge a portion of the solution, and use the clear supernatant. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L1 

Column temperature: 50 ± 5° 

Flow rate: 2.0 mL/min 

Injection volume: 20 µL 

System suitability 

Samples: System suitability solution and Standard solution 

Suitability requirements 

Resolution: NLT 2.0 between prochlorperazine related compound A and prochlorperazine, System suitability solution Relative standard deviation: NMT 5.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of any individual specified or unspecified impurity in the portion of Tablets taken: 

Result = (r_U/r_S) × (C_S/C_U) × (M_R1/M_R2) × (1/F) × 100 

r_U = peak response of each corresponding impurity from the Sample solution 

r_S = peak response of prochlorperazine from the Standard solution

C_S = concentration of USP Prochlorperazine Maleate RS in the Standard solution (mg/mL) 

C_U = nominal concentration of prochlorperazine in the Sample solution (mg/mL) 

M_R1 = molecular weight of prochlorperazine, 373.94

M_R2 = molecular weight of prochlorperazine maleate, 606.09  

F = relative response factor (see Table 2) 

Acceptance criteria: See Table 2. 

Table 2 

a Disregard.

b 2-Chloro-10-[3-(4-methylpiperazin-1-yl)propyl]-10H-phenothiazine sulfoxide. 

c 10-[3-(4-Methylpiperazin-1-yl)propyl]-10H-phenothiazine. 

d Process impurity controlled in the drug substance. It is included for identification purposes only. It should not be reported for the drug product, and should not be included in the total impurities. 

e 4-Chloro-10H-phenothiazine. 

f 2-Chloro-10H-phenothiazine. 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in well-closed containers, protected from light. Store at controlled room temperature. 

Add the following: 

Labeling: When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.   filtrate USP Reference Standards 〈11〉 

USP Prochlorperazine Maleate RS 

USP Prochlorperazine Related Compound A RS 

4-Chloro-10-[3-(4-methylpiperazin-1-yl)propyl]-10H-phenothiazine dihydrochloride. 

C₂₀H₂₄ClN₃S. 2HCl 446.86