Prochlorperazine Maleate

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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C₂₀H₂₄ClN₃S₄· 2C₄H₄O 606.09 

10H-Phenothiazine, 2-chloro-10-[3-(4-methyl-1-piperazinyl)propyl]-, (Z)-2-butenedioate (1:2); 

2-Chloro-10-[3-(4-methylpiperazin-1-yl)propyl]phenothiazine maleate (1:2) CAS RN®: 84-02-6; UNII: I1T8O1JTL6. 

1 DEFINITION 

Prochlorperazine Maleate contains NLT 98.0% and NMT 102.0% of prochlorperazine maleate (C₂₀H₂₄ClN₃S₄· 2C₄H₄O), calculated on the dried basis. 

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

2 IDENTIFICATION 

Change to read: 

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or 197K.

B. The retention time 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. Sonicate to dissolve, if needed, prior to nal dilution. Sample solution: 0.2 mg/mL of Prochlorperazine Maleate in Mobile phase. Sonicate to dissolve, if needed, prior to nal dilution. Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 3.9-mm × 30-cm; 10-µm packing L1 or 4.6-mm × 25-cm; 5-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 0.73% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of prochlorperazine maleate (C₂₀H₂₄ClN₃S₄· 2C₄H₄O) in the portion of Prochlorperazine Maleate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of prochlorperazinefrom 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 = concentration of Prochlorperazine Maleate in the Sample solution (mg/mL)

 Acceptance criteria: 98.0%–102.0% on the dried basis 

4 IMPURITIES 

Residue on Ignition 〈281〉: NMT 0.1% 

Organic Impurities 

Buffer: 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 L of solution. 

Solution A: Buffer 

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 each of USP Prochlorperazine Maleate RS and USP Prochlorperazine Related Compound A RS in Diluent from the Standard stock solution and the Impurity stock solution, respectively 

Standard solution: 6.4 µg/mL of USP Prochlorperazine Maleate RS in Diluent from the Standard stock solution 

Sensitivity solution: 0.32 µg/mL of USP Prochlorperazine Maleate RS in Diluent from the Standard solution 

Sample solution: 0.64 mg/mL of Prochlorperazine Maleate in Diluent 

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, Standard solution, and Sensitivity 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 

Signal-to-noise ratio: NLT 10, Sensitivity solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each individual impurity in the portion of Prochlorperazine Maleate taken: 

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

r_U = peak response of each 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 = concentration of Prochlorperazine Maleate 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. Disregard any peak below 0.05%. 

Table 2 

a F values are based on the response of prochlorperazine (free base). 

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

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

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

e 4-Chloro-10H-phenothiazine. 

f 2-Chloro-10H-phenothiazine. 

5 SPECIFIC TESTS 

Loss on Drying 〈731〉 

Analysis: Dry under vacuum at 60° for 2 h. 

Acceptance criteria: NMT 0.5% 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight, light-resistant containers. Store at room temperature. 

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 443.47