{"id":3454,"date":"2025-09-24T13:51:53","date_gmt":"2025-09-24T06:51:53","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=3454"},"modified":"2025-10-02T14:32:49","modified_gmt":"2025-10-02T07:32:49","slug":"bacitracin","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/bacitracin\/","title":{"rendered":"Bacitracin"},"content":{"rendered":"

(Ph. Eur. monograph 0465)<\/em><\/p>\n

1405-87-4<\/p>\n

Action and use<\/strong><\/p>\n

Polypeptide antibacterial.<\/p>\n

DEFINITION<\/h2>\n

Mixture of antimicrobial polypeptides produced by certain strains of Bacillus licheniformis or Bacillus subtilis, the main components being:<\/p>\n

\u2014 4,10-anhydro[N-[[(4R)-2-[(1S,2S)-1-amino-2-methylbutyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin A);<\/p>\n

\u2014 4,10-anhydro[N-[[(4R)-2-[(1S)-1-amino-2-methylpropyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin B1);<\/p>\n

\u2014 4,10-anhydro[N-[[(4R)-2-[(1S,2S)-1-amino-2-methylbutyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-valyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin B2);<\/p>\n

\u2014 4,10-anhydro[N-[[(4R)-2-[(1S,2S)-1-amino-2-methylbutyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-
\nglutamyl-L-valyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin B3).<\/p>\n

Content<\/h3>\n

Minimum 60 IU\/mg (dried substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

White or almost white, hygroscopic powder.<\/p>\n

Solubility<\/h3>\n

Freely soluble in water and in ethanol (96 per cent).<\/p>\n

IDENTIFICATION<\/h2>\n

First identification: B, C.<\/p>\n

Second identification: A, C.<\/p>\n

A. Thin-layer chromatography (2.2.27).<\/p>\n

Test solution: Dissolve 10 mg of the substance to be examined in a 3.4 g\/L solution of hydrochloric acid R and dilute to 1.0 mL with the same solution.<\/p>\n

Reference solution: Dissolve 10 mg of bacitracin zinc CRS in a 3.4 g\/L solution of hydrochloric acid R and dilute to 1.0 mL with the same solution.<\/p>\n

Plate: TLC silica gel plate R.<\/p>\n

Mobile phase: glacial acetic acid R, water R, butanol R (14:29:57 V\/V\/V).<\/p>\n

Application: 10 \u03bcL.<\/p>\n

Development: Over half of the plate.<\/p>\n

Drying: At 100-105 \u00b0C.<\/p>\n

Detection: Spray with ninhydrin solution R1 and heat at 110 \u00b0C for 5 min.<\/p>\n

Results: The spots in the chromatogram obtained with the test solution are similar in position, size and colour to the spots in the chromatogram obtained with the reference solution.<\/p>\n

B. Composition (see Tests).<\/p>\n

C. Ignite 0.2 g. There is no significant yellow-coloured residue at high temperature. Allow to cool. Dissolve the residue in 0.1 mL of dilute hydrochloric acid R. Add 5 mL of water R and 0.2 mL of strong sodium hydroxide solution R. No white precipitate is formed.<\/p>\n

TESTS<\/h2>\n

Solution S<\/h3>\n

Dissolve 0.25 g in carbon dioxide-free water R and dilute to 25 mL with the same solvent.<\/p>\n

Appearance of solution<\/h3>\n

Solution S is clear (2.2.1).<\/p>\n

pH (2.2.3)<\/h3>\n

6.0 to 7.0 for solution S.<\/p>\n

Composition<\/h3>\n

Liquid chromatography (2.2.29): use the normalisation procedure. Prepare the solutions immediately before use.<\/p>\n

Solution A: 40 g\/L solution of sodium edetate R adjusted to pH 7.0 with dilute sodium hydroxide solution R.<\/p>\n

Solution B: In a volumetric flask, dissolve 54.4 g of potassium dihydrogen phosphate R in water for chromatography R and dilute to 2000 mL with the same solvent. Adjust to pH 6.0 with a 34.8 g\/L solution of dipotassium hydrogen phosphate R and filter through a membrane filter (nominal pore size 0.45 \u03bcm).<\/p>\n

Test solution: Dissolve 0.100 g of the substance to be examined in the mobile phase and dilute to 50.0 mL with the mobile phase.<\/p>\n

Reference solution (a): Dissolve 20.0 mg of bacitracin for system suitability CRS in solution A and dilute to 10.0 mL with the same solution.<\/p>\n

Reference solution (b): Dilute 5.0 mL of reference solution (a) to 100.0 mL with solution A. Dilute 1.0 mL of this solution to 10.0 mL with solution A.<\/p>\n

Reference solution (c) In order to prepare impurities E, F, G and H in situ, heat about 4 mL of reference solution (a) in a water-bath for 30 min. Cool to room temperature.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.15 m, \u00d8 = 4.6 mm;<\/p>\n

\u2014 stationary phase: base-deactivated end-capped octadecylsilyl silica gel for chromatography R (3 \u03bcm);<\/p>\n

\u2014 temperature: 28 \u00b1 2 \u00b0C.<\/p>\n

Mobile phase: acetonitrile R, solution B, water for chromatography R, methanol R (43:100:300:557 V\/V\/V\/V).<\/p>\n

Flow rate: 1.0 mL\/min.<\/p>\n

Detection: Spectrophotometer at 254 nm.<\/p>\n

Injection: 100 \u03bcL of the test solution and reference solutions (a) and (b).<\/p>\n

Run time: 3 times the retention time of bacitracin A.<\/p>\n

Identification of peaks: Use the chromatogram obtained with reference solution (a) to identify the peaks due to impurity M and bacitracins A, B1, B2 and B3 (see Figure 0465.-1).<\/p>\n

Relative retention: With reference to bacitracin A (retention time = about 20 min): impurity A = about 0.44; impurity B = about 0.52; impurity C = about 0.55; bacitracin B1 = about 0.65; bacitracin B2 = about 0.67; bacitracin B3 = about 0.81; impurity M = about 0.87; impurity N = about 0.90; impurity L = about 0.93; impurity O = about 1.2; impurities P and Q = about 1.3; impurity F = about 1.6; impurity G = about 1.8; impurity H = about 2.1; impurity E = about 2.8. If necessary, adjust the composition of the mobile phase by changing the amount of organic modifier whilst keeping the ratio constant between methanol and acetonitrile.<\/p>\n

System suitability:<\/p>\n

\u2014 peak-to-valley ratio: minimum 1.2, where Hp = height above the baseline of the peak due to bacitracin B2 and<\/p>\n

Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to bacitracin B1 in the chromatogram obtained with reference solution (a);<\/p>\n

\u2014 peak-to-valley ratio: minimum 1.1, where Hp = height above the baseline of the peak due to impurity M and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to bacitracin B3 in the chromatogram obtained with reference solution (a);<\/p>\n

\u2014 signal-to-noise ratio: minimum 50 for the peak due to bacitracin A in the chromatogram obtained with reference solution (b).<\/p>\n

Limits:<\/p>\n

\u2014 bacitracin A: minimum 45.0 per cent;<\/p>\n

\u2014 sum of bacitracins A, B1, B2 and B3: minimum 77.0 per cent;<\/p>\n

\u2014 reporting threshold: 0.25 per cent.<\/p>\n

\"Bacitracin\"<\/p>\n

1. impurity A;\u00a0 2. impurity B;\u00a0 3. impurity C;\u00a0 4. bacitracin B1;\u00a0 5. bacitracin B2;\u00a0 6. bacitracin B3;\u00a0 7. impurity M;\u00a0 8. impurity N;\u00a0 9. impurity L;\u00a0 10. bacitracin A; 11. impurity O;\u00a0 12. impurities P and Q;\u00a0 13. impurity F;\u00a0 \u00a014. impurity G;\u00a0 15. impurity H;\u00a0 16. impurity E<\/p>\n

Figure 0465.-1. \u2013 Chromatogram for the test for composition of bacitracin: test solution<\/p>\n

Related substances<\/h3>\n

Liquid chromatography (2.2.29) as described in the test for composition with the following modifications. Use the normalisation procedure.<\/p>\n

Injection: Test solution and reference solutions (a), (b) and (c).<\/p>\n

Identification of impurities: Use the chromatogram obtained with reference solution (a) to identify the peaks due to impurities A, B, C, L, M, N, O, P and Q (see Figure 0465.-1); use the chromatogram obtained with reference solution (c) to identify the peaks due to impurities E, F, G and H (see Figure 0465.-2).<\/p>\n

Limits:<\/p>\n

\u2014 sum of impurities L and N: maximum 8.0 per cent;<\/p>\n

\u2014 impurity E: maximum 4.0 per cent;<\/p>\n

\u2014 impurity A: maximum 3.5 per cent;<\/p>\n

\u2014 impurities B, M: for each impurity, maximum 3.0 per cent;<\/p>\n

\u2014 impurity C: maximum 2.5 per cent;<\/p>\n

\u2014 sum of impurities O, P and Q: maximum 2.5 per cent;<\/p>\n

\u2014 sum of impurities F and G: maximum 2.0 per cent;<\/p>\n

\u2014 impurity H: maximum 1.0 per cent;<\/p>\n

\u2014 any other impurity: for each impurity, maximum 2.0 per cent;<\/p>\n

\u2014 total: maximum 23.0 per cent;<\/p>\n

\u2014 reporting threshold: 0.25 per cent.<\/p>\n

\"Bacitracin\"<\/p>\n

1. impurity F;\u00a0 2. impurity G;\u00a0 3. impurity H;\u00a0 \u00a04. impurity E<\/p>\n

Figure 0465.-2. \u2013 Chromatogram for the test for related substances of bacitracin: reference solution (c)<\/p>\n

Loss on drying (2.2.32)<\/h3>\n

Maximum 5.0 per cent, determined on 1.000 g by drying in vacuo at 60 \u00b0C at a pressure not exceeding 0.1 kPa for 3 h.<\/p>\n

Sulfated ash (2.4.14)<\/h3>\n

Maximum 1.0 per cent, determined on 1.0 g.<\/p>\n

ASSAY<\/h2>\n

Carry out the microbiological assay of antibiotics (2.7.2). Use bacitracin zinc CRS as the reference substance.<\/p>\n

STORAGE<\/h2>\n

In an airtight container at 2 \u00b0C to 8 \u00b0C. If the substance is sterile, the container is also sterile and tamper-evident.<\/p>\n

IMPURITIES<\/h2>\n

Specified impurities A, B, C, E, F, G, H, L, M, N, O, P, Q.<\/p>\n

Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other\/unspecified impurities. It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use) D, I, J, K.<\/p>\n

\"Bacitracin\"<\/p>\n

A. 4,10-anhydro[N-[[(4R)-2-[(1S)-1-amino-2-methylpropyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-valyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin D1, bacitracin C2),<\/p>\n

\"Bacitracin\"<\/p>\n

B. 4,10-anhydro[N-[[(4R)-2-[(1S)-1-amino-2-methylpropyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-valyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin D2, bacitracin C3),<\/p>\n

\"Bacitracin\"<\/p>\n

C. 4,10-anhydro[N-[[(4R)-2-[(1S,2S)-1-amino-2-methylbutyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-valyl-L-lysyl-D-ornithyl-L-valyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin D3, bacitracin C1a),<\/p>\n

\"Bacitracin\"<\/p>\n

D. 4,10-anhydro[N-[[(4R)-2-[(1S)-1-amino-2-methylpropyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-valyl-L-lysyl-D-ornithyl-L-valyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin E),<\/p>\n

\"Bacitracin\"<\/p>\n

E. 4,10-anhydro[N-[[2-[(2S)-2-methyl-1-oxobutyl]-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin F),<\/p>\n

\"Bacitracin\"<\/p>\n

F. 4,10-anhydro[N-[[2-(2-methyl-1-oxopropyl)-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin H1),<\/p>\n

\"Bacitracin\"<\/p>\n

G. 4,10-anhydro[N-[[2-[(2S)-2-methyl-1-oxobutyl]-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-valyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin H2),<\/p>\n

\"Bacitracin\"<\/p>\n

H. 4,10-anhydro[N-[[2-[(2S)-2-methyl-1-oxobutyl]-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-valyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin H3),<\/p>\n

\"Bacitracin\"<\/p>\n

I. 4,10-anhydro[N-[[2-(2-methyl-1-oxopropyl)-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-valyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin I1),<\/p>\n

\"Bacitracin\"<\/p>\n

J. 4,10-anhydro[N-[[2-(2-methyl-1-oxopropyl)-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-valyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin I2),<\/p>\n

\"Bacitracin\"<\/p>\n

K. 4,10-anhydro[N-[[2-[(2S)-2-methyl-1-oxobutyl]-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-valyl-L-lysyl-D-ornithyl-L-valyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin I3),<\/p>\n

\"Bacitracin\"<\/p>\n

L. 4,10-anhydro[N-[[(4R)-2-[(1R,2S)-1-amino-2-methylbutyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin X),<\/p>\n

\"Bacitracin\"<\/p>\n

M. 4,10-anhydro[N-[[2-[(1S,2S)-1-amino-2-methylbutyl]-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin Y),<\/p>\n

\"Bacitracin\"<\/p>\n

N. 4,10-anhydro[N-[[(4S)-2-[(1S,2S)-1-amino-2-methylbutyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin Z),<\/p>\n

\"Bacitracin\"<\/p>\n

O. Mil = 5-methylene-L-isoleucine: 4,10-anhydro[N-[[(4R)-2-[(1S,2S)-1-amino-2-methylbutyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-5-methylene-L-isoleucyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin J1),<\/p>\n

\"Bacitracin\"<\/p>\n

P. Mil = 5-methylene-L-isoleucine: 4,10-anhydro[N-[[(4R)-2-[(1S,2S)-1-amino-2-methylbutyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-5-methylene-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin J2),<\/p>\n

\"Bacitracin\"<\/p>\n

Q. 4,10-anhydro[N-[[(4R)-2-[(1S,2S)-1-amino-2-methylpent-4-en-1-yl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin J3).<\/p>\n","protected":false},"excerpt":{"rendered":"

(Ph. Eur. monograph 0465) 1405-87-4 Action and use Polypeptide antibacterial. DEFINITION Mixture of antimicrobial polypeptides produced by certain strains of Bacillus licheniformis or Bacillus subtilis, the main components being: \u2014 4,10-anhydro[N-[[(4R)-2-[(1S,2S)-1-amino-2-methylbutyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin A); \u2014 4,10-anhydro[N-[[(4R)-2-[(1S)-1-amino-2-methylpropyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin B1); \u2014 4,10-anhydro[N-[[(4R)-2-[(1S,2S)-1-amino-2-methylbutyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1-glutamyl-L-isoleucyl-L-lysyl-D-ornithyl-L-valyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin B2); \u2014 4,10-anhydro[N-[[(4R)-2-[(1S,2S)-1-amino-2-methylbutyl]-4,5-dihydro-1,3-thiazol-4-yl]carbonyl]-L-leucyl-D-\u03b1- glutamyl-L-valyl-L-lysyl-D-ornithyl-L-isoleucyl-D-phenylalanyl-L-histidyl-D-\u03b1-aspartyl-L-asparagine] (bacitracin B3). Content Minimum 60 IU\/mg (dried substance). CHARACTERS Appearance White…<\/p>\n","protected":false},"author":4,"featured_media":3493,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-3454","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicinal-substances"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/3454","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=3454"}],"version-history":[{"count":7,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/3454\/revisions"}],"predecessor-version":[{"id":7884,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/3454\/revisions\/7884"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/3493"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=3454"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=3454"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=3454"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}