Add the following:
Orlistat Capsules
DEFINITION
Orlistat Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of orlistat (C29H53NO5).
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
Mobile phase:
Acetonitrile, phosphoric acid, and water (860: 0.05: 140)
Standard solution:
0.6 mg/mL of USP Orlistat RS in Mobile phase
Sample solution:
Transfer the contents of NLT 10 Capsules into a suitable container, weigh, and mix. Transfer an accurately weighed portion of the powder, equivalent to 120 mg of orlistat, into a 200-mL volumetric flask. Add 140 mL of Mobile phase, and sonicate for 1 min. Shake the resulting solution mechanically for 15 min, and dilute with Mobile phase to volume. Pass a portion of this solution through a filter of 0.45-µm or finer pore size, discarding the first few mL of filtrate.
Chromatographic system
Mode:
LC
Detector:
195 nm
Column:
3.9-mm × 15-cm; packing L1
Flow rate:
1.0 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
System suitability requirements
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of orlistat (C29H53NO5) in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Orlistat RS in the Standard solution (mg/mL) |
| CU | = | = concentration of orlistat in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Medium:
3% Sodium lauryl sulfate and 0.5% sodium chloride in water. To each 10 L of media add 1–2 drops of n-octanol, and adjust with phosphoric acid to a pH of 6.0; 900 mL.
Apparatus 2:
75 rpm, with coil wire sinker
Time:
45 min
Mobile phase:
Acetonitrile and water (860:140)
Standard solution:
Transfer about 13 mg of USP Orlistat RS to a 100-mL volumetric flask. Dissolve in 2 mL of acetonitrile, and dilute with Medium to volume.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.2-µm pore size.
Chromatographic system
Mode, Detector, and Column:
Proceed as directed in the Assay.
Flow rate:
2.0 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
System suitability requirements
Relative standard deviation:
NMT 2.0%
Calculate the percentage of the labeled amount of orlistat (C29H53NO5) dissolved:
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = label claim (mg/Capsule) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 75% (Q) of the labeled amount of orlistat is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Mobile phase, Standard solution, and Sample solution:
Prepare as directed in the Assay.
System suitability solution:
0.025 mg/mL of USP Orlistat Related Compound D RS in Mobile phase. Transfer 1 mL of this solution to a 50-mL volumetric flask, and dilute with Standard solution to volume.
Chromatographic system
System suitability
Sample:
System suitability solution
System suitability requirements
Resolution:
NLT 1.4 between USP Orlistat RS and USP Orlistat Related Compound D RS
Relative standard deviation:
NMT 2.0% for the orlistat peak
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each individual impurity in the Sample solution |
| rS | = | = peak response of orlistat in the Standard solution |
| CS | = | = concentration of USP Orlistat RS in the Standard solution (mg/mL) |
| CU | = | = concentration of orlistat in the Sample solution (mg/mL) |
| F | = | = relative response factor (see Impurity Table 1) |
Acceptance criteria:
See Impurity Table 1.
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Orlistat open-ring epimera |
0.45 | 1.0 | 1.5 |
| Orlistat open ringb | 0.5 | 1.0 | 0.3 |
| Orlistat related compound D |
0.9 | 1.0 | 1.0 |
| Orlistat | 1.0 | — | — |
| Hexyl undecyl pyranonec |
2.0 | 1.0 | 0.2 |
| Henicosenyl leucinated | 4.7 | 2.3 | 0.3 |
| Any other identified impurity | — | — | 0.3 |
| Individual unidentified impurity |
— | 1.0 | 0.2 |
| Total impurities | — | — | 3.0 |
|
a
(2S,3R,5S)-5-[(N-Formyl-l-leucyl)oxy]-2-hexyl-3-hydroxyhexadecanoic acid.
b
(2S,3S,5S)-5-[(N-Formyl-l-leucyl)oxy]-2-hexyl-3-hydroxyhexadecanoic acid.
c
(S)-3-Hexyl-5,6-dihydro-6-undecyl-2H-pyran-2-one.
d
(S)-[(S,E)-Henicos-7-en-10-yl] N-formyl-l-leucinate.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers, and store at 25
, excursions permitted between 15 and 30.
, excursions permitted between 15 and 30.
USP35
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Clydewyn M. Anthony, Ph.D.
Senior Scientific Liaison 1-301-816-8139 |
(SM22010) Monographs - Small Molecules 2 |
| 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 4133
Pharmacopeial Forum: Volume No. 35(5) Page 1169