This impurity is not to be reported for the drug product or to be included in total ... b .4-[1-Hydroxy-2-(4-phenylbutylamino)ethyl]-2-(hydroxymethyl)phenol. ⢠PACKAGING AND ... This is a counter ion of salmeterol that is included in this table for identi- ... 396.42 hydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-yl ester.
Accessed from 10.6.1.1 by barce5 on Thu May 26 05:47:03 EDT 2016
4020 Fluticasone / Official Monographs
USP 39 N>
Table 7 (Continued)
Name Fluticasone dimera,j Any unspecified degradation product Total degradation products .
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Relative Retention Time 1.09
100
Acceptance Criteria, NMT (%) —
Table 8 Particle Size Range (µm) 100 Total
— 0.10 —
= total number of particles >100 µm present in the Sample solution Acceptance criteria: See Table 8.
0.2
a This
is a process impurity that is included in this table for identification purposes only. This impurity is controlled in drug substance. This impurity is not to be reported for the drug product or to be included in total degradation products. b 4-[1-Hydroxy-2-(4-phenylbutylamino)ethyl]-2-(hydroxymethyl)phenol. c 4-[1-Hydroxy-2-(6-phenethoxyhexylamino)ethyl]-2-(hydroxymethyl)phenol. d 4-{1-Hydroxy-2-[6-(3-phenylpropoxy)hexylamino]ethyl}-2-(hydroxymethyl)phenol. e 4-{1-Hydroxy-2-[6-(4-phenylbutan-2-yloxy)hexylamino]ethyl}-2-(hydroxymethyl)phenol. f This is a counter ion of salmeterol that is included in this table for identification purposes only. It is not to be reported for the drug product or to be included in the total degradation products. g 4-{1-Hydroxy-2-[6-(4-phenylbutoxy)hexylamino]ethyl}-2-methylphenol. h 6α,9α-Difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carbodithioic acid. i 4-{1-Hydroxy-2-[(2-hydroxy-5-{1-hydroxy-2-[6-(4-phenylbutoxy)hexylamino]ethyl}benzyl)[6-(4-phenylbutoxy)hexyl]amino]ethyl}-2-(hydroxymethyl)phenol. j 6α, 9α-Difluoro-11β,17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene17β-carboxylic acid 6α, 9α-difluoro-17β-(fluoromethylthio)carbonyl-11βhydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-yl ester. .
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SPECIFIC TESTS • MICROBIAL ENUMERATION TESTS 〈61〉 and TESTS FOR SPECIFIED MICROORGANISMS 〈62〉: The total aerobic microbial count does not exceed 101 cfu/g of formulation. The total aerobic yeasts and molds count does not exceed 101 cfu/g of formulation. It meets the requirements of the tests for absence of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Salmonella species. • FOREIGN PARTICULATE MATTER The test described below and the specification is only applicable to a microscopic particle count test methodology. Particulate Matter in Injections 〈788〉 describes details of the test apparatus to be used for the determination of particulate matter using a microscopic particle count test methodology. Samples should be carefully prepared to avoid environmental contamination, and testing should be performed with suitable controls, including the appropriate use of blank determinations. Filter: Mixed cellulose and ester; 25-mm diameter and 0.45-µm pore size Sample solution: Perform testing on two previously unused inhalers. Prime each inhaler by discharging a predetermined number of actuations to waste. Discharge, and dissolve 16 actuations, eight from each of two canisters in 50 mL of methanol. Analysis Sample: Sample solution Pass the Sample solution through the Filter, and allow the Filter to dry under conditions that will limit particulate contamination. Using a microscopic particle count test method, enumerate the number of particles present in the Sample solution. Calculate the number of particles per actuation:
Number of Particles per Actuation 140 50 5 185
ADDITIONAL REQUIREMENTS • PACKAGING AND STORAGE: Preserve in nonreactive, lightresistant aerosol containers with metered valves fitted with a dose counter and provided with oral inhalation actuators. Avoid exposure to heat. Store at controlled room temperature. • USP REFERENCE STANDARDS 〈11〉 USP Fluticasone Propionate RS USP Fluticasone Propionate Related Compound D RS S-Methyl 6α, 9α-difluoro-11β-hydroxy-16α-methyl3-oxo-17α-propionyloxyandrosta-1,4-diene-17βcarbothioate. C25H32F2O5S 482.58 USP Fluticasone Propionate Related Compound J RS 6α, 9α-Difluoro-11β,17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid. C21H26F2O5 396.42 USP Salmeterol Xinafoate RS ▲USP39
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USP Monographs
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Result = (N100 µm present in the Sample solution Acceptance criteria: See Table 5. Table 5
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0.1 1.3
a This
is a process impurity that is included in this table for identification only. This impurity is controlled in the drug substance. This impurity is not to be reported for the drug product or to be included in the total degradation products. b 4-[1-Hydroxy-2-(4-phenylbutylamino)ethyl]-2-(hydroxymethyl)phenol. c 4-[1-Hydroxy-2-(6-phenethoxyhexylamino)ethyl]-2-(hydroxymethyl)phenol. d 4-{1-Hydroxy-2-[6-(3-phenylpropoxy)hexylamino]ethyl}-2-(hydroxymethyl)phenol. e 4-{1-Hydroxy-2-[6-(4-phenylbutan-2-yloxy)hexylamino]ethyl}-2-(hydroxymethyl)phenol. f This is a counter ion of salmeterol that is included in this table for identification only. It is not to be reported for the drug product or to be included in the total degradation products. g 4-{1-Hydroxy-2-[6-(4-phenylbutoxy)hexylamino]ethyl}-2-methylphenol. h 6α,9α-Difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carbodithioic acid. i 4-{1-Hydroxy-2-[(2-hydroxy-5-{1-hydroxy-2-[6-(4-phenylbutoxy)hexylamino]ethyl}benzyl)[6-(4-phenylbutoxy)hexyl]amino]ethyl}-2-(hydroxymethyl)phenol. j 6α, 9α-Difluoro-11β,17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene17β-carboxylic acid 6α, 9α-difluoro-17β-(fluoromethylthio)carbonyl-11βhydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-yl ester. .
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USP Monographs
100
SPECIFIC TESTS • MICROBIAL ENUMERATION TESTS 〈61〉 and TESTS FOR SPECIFIED MICROORGANISMS 〈62〉: The total aerobic microbial count does not exceed 101 cfu/g of powder. The total aerobic yeasts and molds count does not exceed 101 cfu/ g of formulation. It meets the requirements of the tests for absence of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Salmonella species. • FOREIGN PARTICULATE MATTER Particulate Matter in Injections 〈788〉 describes details of the test apparatus to be used for the determination of particulate matter using a microscopic particle count test methodology. Samples should be carefully prepared to avoid environmental contamination, and testing should be performed with suitable controls, including the appropriate use of blank determinations. Diluent: Methanol and water (65:35) passed through a filter of 0.45-µm pore size Filter: Mixed cellulose and ester filter; 25-mm diameter and 0.45-µm pore size Sample solution: Transfer contents of NLT 8 unit doses to a suitable container. Dissolve in 75 mL of Diluent. Analysis Sample: Sample solution Pass the Sample solution through the filter and allow the filter to dry under conditions that will limit particulate contamination. Using a microscopic particle count test method, enumerate the number of particles present in the Sample solution. Calculate the total number of particles per actuation by the formula:
Number of Particles/Dose (NMT) 200 100 10 300
ADDITIONAL REQUIREMENTS • PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store at controlled room temperature, in a dry place away from direct heat or sunlight. • USP REFERENCE STANDARDS 〈11〉 USP Fluticasone Propionate RS USP Fluticasone Propionate Related Compound D RS S-Methyl 6α, 9α-difluoro-11β-hydroxy-16α-methyl3-oxo-17-propionyloxyandrosta-1,4-diene-17αcarbothioate. C25H32F2O5S 482.58 USP Fluticasone Propionate Related Compound J RS 6α, 9α-Difluoro-11β,17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid. C21H26F2O5 396.42 USP Salmeterol Related Compound H RS 1-Hydroxy-4-[2-hydroxy-5-(1-hydroxy-2-{ [6-(4-phenylbutoxy)hexyl]amino}ethyl)benzyl]2-naphthoic acid. C36H43NO6 585.73 USP Salmeterol Xinafoate RS ▲USP39
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Result = (N100)/8 N
