Rivastigmine Tartrate Capsules
DEFINITION
Rivastigmine Tartrate Capsules contain an amount of Rivastigmine Tartrate equivalent to NLT 94.0% and NMT 105.0% of the labeled amount of rivastigmine (C14H22N2O2).
IDENTIFICATION
• The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Buffer:
8.6 mg/mL of monobasic ammonium phosphate in water. Adjust with ammonia solution to a pH of 7.0.
Mobile phase:
Methanol, acetonitrile, and Buffer (15:15:70)
Standard solution:
0.064 mg/mL of USP Rivastigmine Tartrate RS in Mobile phase. [Note—Use a small amount of methanol (about 2% of the final volume) to facilitate dissolution before diluting with Mobile phase to volume, and use sonication if necessary. ]
System suitability solution:
0.01 mg/mL each of USP Rivastigmine Related Compound A RS and USP Rivastigmine Related Compound B RS in Mobile phase
Sample solution:
Remove as completely as possible the contents of NLT 20 Capsules, and mix. Transfer a weighed portion of the combined contents, equivalent to about 48 mg of rivastigmine, to a 250-mL volumetric flask. Add 25 mL of methanol and 60 mL of Mobile phase, and sonicate for 15 min to disperse the contents. Dilute with Mobile phase to volume, mix well, and centrifuge. Dilute a portion of the supernatant with Mobile phase to obtain a solution having a concentration of 0.038 mg/mL of rivastigmine, based on the label claim.
Chromatographic system
Mode:
LC
Detector:
UV 215 nm
Column:
4.6-mm × 25-cm; 5-µm packing L7
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Samples:
Standard solution and System suitability solution
[Note—The relative retention times for rivastigmine related compound A, rivastigmine related compound B, and rivastigmine are 0.46, 0.57, and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 1.5 between rivastigmine related compound A and rivastigmine related compound B, System suitability solution
Column efficiency:
NLT 5000 theoretical plates, Standard solution
Tailing factor:
NMT 2.3, Standard solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C14H22N2O2 in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of rivastigmine from the Sample solution |
| rS | = | = peak response of rivastigmine from the Standard solution |
| CS | = | = concentration of USP Rivastigmine Tartrate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of rivastigmine in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of rivastigmine, 250.34 |
| Mr2 | = | = molecular weight of rivastigmine tartrate, 400.42 |
Acceptance criteria:
94.0%–105.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Medium:
Water; 500 mL, deaerated
Apparatus 2:
50 rpm, with sinkers, if necessary
Time:
30 min
Buffer, Mobile phase, and System suitability solution:
Prepare as directed in the Assay.
Standard solution:
0.192 mg/mL of USP Rivastigmine Tartrate RS in Mobile phase. Further dilute with Medium to obtain a solution having a concentration similar to that expected in the Sample solution.
Sample solutions:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first few mL.
Chromatographic system and System suitability:
Proceed as directed in the Assay.
[Note—Use an injection size of 100 µL. ]
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C14H22N2O2 dissolved:
Result = (rU/rS) × CS × (Mr1/Mr2) × (V/L) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| Mr1 | = | = molecular weight of rivastigmine, 250.34 |
| Mr2 | = | = molecular weight of rivastigmine tartrate, 400.42 |
| V | = | = volume of Medium (mL), 500 |
| L | = | = Capsule label claim (mg) |
Tolerances:
NLT 75% (Q) of the labeled amount of C14H22N2O2 is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Buffer, Mobile phase, and System suitability solution:
Prepare as directed in the Assay.
Standard solution:
1.6 µg/mL of USP Rivastigmine Tartrate RS in Mobile phase
Sample solution:
Remove as completely as possible the contents of NLT 20 Capsules, and mix. Transfer a weighed portion of the combined contents, equivalent to 25 mg of rivastigmine, to a 25-mL volumetric flask. Disperse in 10 mL of Mobile phase, and sonicate for 15 min. Dilute with Mobile phase to volume, mix well, and centrifuge. Use the supernatant.
Chromatographic system:
Proceed as directed in the Assay.
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 1.5 between rivastigmine related compound A and rivastigmine related compound B, System suitability solution
Relative standard deviation:
NMT 10.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
[Note—Identify the peaks using the relative retention times provided in Impurity Table 1. ]
Calculate the percentage of each impurity in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × (1/F) × 100
| rU | = | = peak response of each individual impurity from the Sample solution |
| rS | = | = peak response of rivastigmine from the Standard solution |
| CS | = | = concentration of USP Rivastigmine Tartrate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of rivastigmine in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of rivastigmine, 250.34 |
| Mr2 | = | = molecular weight of rivastigmine tartrate, 400.42 |
| F | = | = relative response factor (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 1.0%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|
|---|---|---|---|---|
| Phenol impuritya | 0.28 | 1.6 | 0.6 | |
| Rivastigmine | 1.0 | 1.0 | — | |
| Any other individual impurity | — | 1.0 | 0.2 | |
| Total impurities | — | — | 1.0 | |
|
a
(S)-3-[1-(Dimethylamino)ethyl]phenol.
|
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ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers, and store at controlled room temperature.
• USP Reference Standards 11
11
USP Rivastigmine Tartrate RS
USP Rivastigmine Related Compound A RS
Di-p-toluoyl-d-(+)-tartaric acid monohydrate.
C20H20O9 404.37
Di-p-toluoyl-d-(+)-tartaric acid monohydrate.
C20H20O9 404.37
USP Rivastigmine Related Compound B RS
N,N-Dimethylcarbamic acid-3-[1-(dimethylamino)ethyl]phenyl ester.
C13H20N2O2 236.32
N,N-Dimethylcarbamic acid-3-[1-(dimethylamino)ethyl]phenyl ester.
C13H20N2O2 236.32
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Elena Gonikberg, Ph.D.
Principal Scientific Liaison 1-301-816-8251 |
(SM32010) Monographs - Small Molecules 3 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4581
Pharmacopeial Forum: Volume No. 36(1) Page 131