Loratadine Oral Solution
DEFINITION
Loratadine Oral Solution contains NLT 94.0% and NMT 105.0% of the labeled amount of loratadine (C22H23ClN2O2).
IDENTIFICATION
•  A. Thin-Layer Chromatographic Identification Test 201
Standard solution:  5 mg/mL of USP Loratadine RS in dichloromethane
Sample solution:  Place a volume of Oral Solution, equivalent to 10 mg of loratadine, in a centrifuge tube. Add 10 mL of 0.2 N sodium hydroxide and 2.0 mL of dichloromethane. Rotate the centrifuge tube for 10 min, centrifuge, and discard the aqueous phase.
Developing solvent system:  Ethyl ether and diethylamine (40:1), in a paper-lined tank
Acceptance criteria:  Meets the requirements
•  B. 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:  6.8 g/L of monobasic potassium phosphate in water, adjusted with phosphoric acid to a pH of 3.0 ± 0.1
Mobile phase:  Acetonitrile and Buffer (3:7)
Diluent:  Acetonitrile and water (3:7)
Internal standard solution:  0.3 mg/mL of butylparaben in Diluent
Standard stock solution:  1.0 mg/mL of USP Loratadine RS in acetonitrile
Standard solution:  Transfer 5.0 mL of Internal standard solution, 5.0 mL of Standard stock solution, and 12 mL of water to a 50-mL volumetric flask. Dilute with Diluent to volume.
Sample solution:  Transfer a portion of Oral Solution, nominally equivalent to 5 mg of loratadine, to a 50-mL volumetric flask. Pipet 5.0 mL of Internal standard solution into the flask, and dilute with Diluent to volume.
Chromatographic system 
Mode:  LC
Detector:  UV 254 nm
Column:  4-mm × 30-cm; 10-µm packing L11
Column temperature:  20–30
Flow rate:  2 mL/min
Injection size:  10 µL
System suitability 
Sample:  Standard solution
[Note—The relative retention times for butylparaben and loratadine are about 0.78 and 1.0, respectively. ]
Suitability requirements 
Resolution:  NLT 1.9 between loratadine and butylparaben
Tailing factor:  NMT 1.6 for the loratadine and butylparaben peaks
Relative standard deviation:  NMT 2%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of the labeled amount of loratadine (C22H23ClN2O2) in the portion of Oral Solution taken:
Result = (RU/RS) × (CS/CU) × 100
RU== peak response ratio of loratadine to the internal standard from the Sample solution
RS== peak response ratio of loratadine to the internal standard from the Standard solution
CS== concentration of USP Loratadine RS in the Standard solution (mg/mL)
CU== nominal concentration of loratadine in the Sample solution (mg/mL)
Acceptance criteria:  94.0%–105.0%
PERFORMANCE TESTS
•  Deliverable Volume 698: Meets the requirements
IMPURITIES
•  Organic Impurities
Mobile phase:  4.3 g/L of sodium dodecyl sulfate in a mixture of acetonitrile and water (1:1). Adjust with phosphoric acid to a pH of 2.6 ± 0.1.
Diluent:  Mobile phase and water (2:1)
System suitability solution 1:  2 µg/mL of USP Loratadine RS in Diluent
System suitability solution 2:  0.2 µg/mL of USP Loratadine RS in Diluent from System suitability solution 1
System suitability solution 3:  Transfer an amount of Oral Solution, equivalent to 20 mg of loratadine, into a screw-cap glass container. Add 1 mL of 3% aqueous hydrogen peroxide, and mix. Cap, and heat at 65 for 18–24 h. Allow to cool to room temperature, and then dilute 5 mL with Diluent to 25 mL.
Sample solution:  0.2 mg/mL of loratadine from a volume of Oral Solution in Diluent
Chromatographic system 
Mode:  LC
Detector:  UV 254 nm
Column:  4.6-mm × 25-cm; 5-µm packing L7
Column temperature:  30–40
Flow rate:  2 mL/min
Injection size:  50 µL
System suitability 
Samples:  System suitability solution 1, System suitability solution 2, and System suitability solution 3
[Note—See Table 1 for relative retention times. ]
Suitability requirements 
Resolution:  NLT 3.0 between loratadine and 2-hydroxymethyl loratadine, System suitability solution 3
Tailing factor:  0.7–1.1, System suitability solution 1
Relative standard deviation:  NMT 10%, System suitability solution 2
Analysis 
Sample:  Sample solution
Calculate the percentage of each individual related compound in the portion of Oral Solution taken:
Result = (rU/rT) × 100
rU== individual peak response of each related compound in the Sample solution
rT== sum of all the peak responses in the Sample solution, excluding excipient peaks
Acceptance criteria:  See Table 1.
Table 1
Name Relative
Retention
Time
Acceptance
Criteria,
NMT (%)
4-Hydroxymethyl loratadinea 0.70 0.3
2-Hydroxymethyl loratadineb 0.84 0.3
Loratadine 1.0
Any other individual impurity 0.2
Total impurities 0.5
a  Ethyl 4-[8-chloro-5,6-dihydro-4-(hydroxymethyl)-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene]-1-piperidinecarboxylate.
b  Ethyl 4-[8-chloro-5,6-dihydro-2-(hydroxymethyl)-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene]-1-piperidinecarboxylate.
SPECIFIC TESTS
•  Microbial Enumeration Tests 61 and Tests for Specified Microorganisms 62: The total aerobic microbial count is NMT 102 cfu/mL, and the total combined molds and yeasts count is NMT 5 × 101 cfu/mL. It meets the requirements for the absence of Salmonella species and Escherichia coli.
Change to read:
•  pH 791: 2.2(RB 1-May-2011)–3.1
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in tight containers, and store between 2 and 25.
•  USP Reference Standards 11
USP Loratadine RS Click to View Structure
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Mary S. Waddell
Scientific Liaison
1-301-816-8124
(SM42010) Monographs - Small Molecules 4
61 Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison
1-301-816-8339
(GCM2010) General Chapters - Microbiology
62 Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison
1-301-816-8339
(GCM2010) General Chapters - Microbiology
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 3713
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