Cevimeline Hydrochloride

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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C₁₀H₁₇NOS.HCl · ½ H₂O 244.78 

C₁₀H₁₇NOS 199.31 

Spiro[1-azabicyclo[2.2.2]octane-3,5′-[1,3]oxathiolane], 2′-methyl-,hydrochloride, hydrate (2:1), cis-. 

(±)-cis-2-Methylspiro[1,3-oxathiolane-5,3′-quinuclidine] hydrochloride, hemihydrate. 

(2RS,2’RS)-2’-Methyl-4-azaspiro{bicyclo[2.2.2]octane-2,5’-[1,3]oxathiolane} hydrochloride hemihydrate CAS RN®: 153504-70-2; UNII:  P81Q6V85NP. 

Free base CAS RN®: 107233-08-9; UNII: K9V0CDQ56E. 

1 DEFINITION 

Cevimeline Hydrochloride contains NLT 98.0% and NMT 102.0% of cevimeline hydrochloride (C H NOS · HCl) calculated on the anhydrous basis. 

2 IDENTIFICATION 

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. C. Identification Tests—General 〈191〉, Chemical Identification Tests, Chloride: Meets the requirements 

3 ASSAY 

Procedure 

Solution A: To each liter of water, add 1.0 mL of phosphoric acid and 1.0 g of sodium 1-hexanesulfonate monohydrate. Solution B: To each liter of acetonitrile, add 1.0 mL of phosphoric acid. 

Mobile phase: See Table 1. 

Table 1 

Diluent: Acetonitrile and water (50:50) 

System suitability solution: 0.022 mg/mL of USP Cevimeline trans-Isomer RS and 7.4 mg/mL of USP Cevimeline Hydrochloride RS in Diluent Standard solution: 0.2 mg/mL of USP Cevimeline Hydrochloride RS in Diluent. Sonication may be used to promote dissolution. Sample solution: 0.2 mg/mL of Cevimeline Hydrochloride in Diluent. Sonication may be used to promote dissolution.

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 200 nm 

Column: 2.1-mm × 5-cm; 1.7-µm packing L1 

Column temperature: 60° 

Flow rate: 0.7 mL/min 

Injection volume: 1 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—See Table 2 for the relative retention times.] 

Suitability requirements 

Resolution: NLT 1.5 between cevimeline and cevimeline trans-isomer, System suitability solution 

Tailing factor: NMT 2.0, Standard solution 

Relative standard deviation: NMT 0.73%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of cevimeline hydrochloride (C₁₀H₁₇NOS.HCl) in the portion of Cevimeline Hydrochloride taken:  

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of cevimeline from the Sample solution 

r_S = peak response of cevimeline from the Standard solution 

C_S = concentration of USP Cevimeline Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Cevimeline Hydrochloride in the Sample solution (mg/mL)

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

4 IMPURITIES 

Residue on Ignition 〈281〉: NMT 0.1% 

Organic Impurities 

Solution A, Solution B, Mobile phase, Diluent, System suitability solution, and Chromatographic system: Proceed as directed in the Assay. Standard stock solution: 0.44 mg/mL of USP Cevimeline Hydrochloride RS in Diluent. Sonication may be used to promote dissolution. Standard solution: 0.022 mg/mL of USP Cevimeline Hydrochloride RS from Standard stock solution in Diluent. Sonication may be used to promote dissolution. 

Sensitivity solution: 0.011 mg/mL of USP Cevimeline Hydrochloride RS from Standard solution in Diluent 

Sample solution A: 7.4 mg/mL of Cevimeline Hydrochloride in Diluent. Sonication may be used to promote dissolution. Sample solution B: 22.1 mg/mL of Cevimeline Hydrochloride in Diluent. Sonication may be used to promote dissolution. System suitability 

Samples: System suitability solution, Standard solution, and Sensitivity solution 

[Note—See Table 2 for the relative retention times.] 

Suitability requirements 

Resolution: NLT 1.5 between cevimeline and cevimeline trans-isomer, System suitability solution 

Relative standard deviation: NMT 5.0%, Standard solution 

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

Analysis 

Samples: Standard solution, Sample solution A, and Sample solution B 

Calculate the percentage of cevimeline trans-isomer in the portion of Cevimeline Hydrochloride taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of cevimeline trans-isomer from the Sample solution 

r_S = peak response of cevimeline from the Standard solution 

C_S = concentration of USP Cevimeline Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Cevimeline Hydrochloride in the Sample solution (mg/mL)

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

Calculate the percentage of any unspecified impurity in the portion of Cevimeline Hydrochloride taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

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

r_S = peak response of cevimeline from the Standard solution 

C_S = concentration of USP Cevimeline Hydrochloride RS in the Standard solution (mg/mL) 

C_U = concentration of Cevimeline Hydrochloride in the Sample solution (mg/mL) 

Acceptance criteria: See Table 2. The reporting threshold is 0.05%. 

Table 2 

^a This peak is due to the chloride counterion; hence it is not an impurity. It is not to be reported or included in the Total impurities. b(2RS,2′SR)-2′-Methyl-4-azaspiro{bicyclo[2.2.2]octane-2,5′-[1,3]oxathiolane}. 

5 SPECIFIC TESTS 

Water Determination 〈921〉, Method I, Method Ic: 3.2%–4.50% 

6 ADDITIONAL REQUIREMENTS 

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

USP Reference Standards 〈11〉 

USP Cevimeline Hydrochloride RS 

USP Cevimeline trans-Isomer RS 

(2RS,2′SR)-2′-Methyl-4-azaspiro{bicyclo[2.2.2]octane-2,5′-[1,3]oxathiolane}hydrochloride hemihydrate. 

C₁₀H₁₇NOS.HCl · ½ H₂O 244.78