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Chemistry

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Also known as: 77-92-9, 2-hydroxypropane-1,2,3-tricarboxylic acid, Citric acid, anhydrous, Aciletten, Anhydrous citric acid, Citro
Molecular Formula
C6H8O7
Molecular Weight
192.12  g/mol
InChI Key
KRKNYBCHXYNGOX-UHFFFAOYSA-N
FDA UNII
XF417D3PSL

Citric Acid
A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability.
Anhydrous citric acid is a Calculi Dissolution Agent and Anti-coagulant. The mechanism of action of anhydrous citric acid is as an Acidifying Activity and Calcium Chelating Activity. The physiologic effect of anhydrous citric acid is by means of Decreased Coagulation Factor Activity.
1 2D Structure

Citric Acid

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
2-hydroxypropane-1,2,3-tricarboxylic acid
2.1.2 InChI
InChI=1S/C6H8O7/c7-3(8)1-6(13,5(11)12)2-4(9)10/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)
2.1.3 InChI Key
KRKNYBCHXYNGOX-UHFFFAOYSA-N
2.1.4 Canonical SMILES
C(C(=O)O)C(CC(=O)O)(C(=O)O)O
2.2 Other Identifiers
2.2.1 UNII
XF417D3PSL
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Anhydrous Citric Acid

2. Citrate

3. Citric Acid Monohydrate

4. Citric Acid, Anhydrous

5. Uralyt U

2.3.2 Depositor-Supplied Synonyms

1. 77-92-9

2. 2-hydroxypropane-1,2,3-tricarboxylic Acid

3. Citric Acid, Anhydrous

4. Aciletten

5. Anhydrous Citric Acid

6. Citro

7. Citretten

8. Chemfill

9. Hydrocerol A

10. 1,2,3-propanetricarboxylic Acid, 2-hydroxy-

11. Citric Acid Anhydrous

12. Kyselina Citronova

13. 2-hydroxy-1,2,3-propanetricarboxylic Acid

14. 2-hydroxytricarballylic Acid

15. Caswell No. 221c

16. 3-carboxy-3-hydroxypentane-1,5-dioic Acid

17. Fema No. 2306

18. F 0001 (polycarboxylic Acid)

19. 2-hydroxypropanetricarboxylic Acid

20. Fema Number 2306

21. K-lyte

22. Kyselina Citronova [czech]

23. K-lyte Ds

24. Citric Acid,anhydrous

25. Ccris 3292

26. Hsdb 911

27. Epa Pesticide Chemical Code 021801

28. Citricum Acidum

29. Citric Acid Monoglyceride

30. Uro-trainer

31. Ai3-06286

32. Suby G

33. Nsc 30279

34. Nsc 626579

35. Brn 0782061

36. Mfcd00011669

37. Nsc-30279

38. Nsc-626579

39. Chembl1261

40. Xf417d3psl

41. Kyselina 2-hydroxy-1,2,3-propantrikarbonova [czech]

42. Kyselina 2-hydroxy-1,2,3-propantrikarbonova

43. Chebi:30769

44. .beta.-hydroxytricarballylic Acid

45. Citr

46. Nsc30279

47. Nsc626579

48. Nsc-112226

49. Citric Acid Bp

50. Citric Acid, 99%

51. Ncgc00090954-03

52. E330

53. 2-hydroxy-1,2,3-propanetricarboxyic Acid

54. Citric Acid,hydrous

55. Dsstox_cid_332

56. E 330

57. Beta-hydroxytricarballylic Acid

58. Citric Acid, Hydrous

59. Citrate Anion

60. Dsstox_rid_75520

61. Dsstox_gsid_20332

62. 141633-96-7

63. 1,2,3-propanetricarboxylic Acid, 2-hydroxy-, Homopolymer

64. Ins No.330

65. Citric Acid [usan:jan]

66. Cas-77-92-9

67. Ins-330

68. 1,3-propanetricarboxylic Acid, 2-hydroxy-

69. 10402-15-0

70. Einecs 201-069-1

71. Unii-xf417d3psl

72. E-330

73. Citraclean

74. Citronensaeure

75. Acidum Citricum

76. Citric-acid

77. Anhydrous Citrate

78. 2fwp

79. 4aci

80. 4nrm

81. H3cit

82. Citric Acid, Anhydrous [usp:jan]

83. Citric Acid,(s)

84. Citric Acid (8ci)

85. K-lyte (salt/mix)

86. 1i2s

87. 1o4l

88. 1rq2

89. 1y4a

90. 2bo4

91. 2c4v

92. 2fw6

93. 4to8

94. Citraclean (salt/mix)

95. Poly(oxy-1,2-ethanediyl), .alpha.-phosphono-.omega.-hydroxy-, C14-18-alkyl Ethers

96. Citric Acid-[13c6]

97. Citric Acid (anhydrous)

98. Spectrum3_001850

99. Wln: Qv1xqvq1vq

100. Beta-hydroxytricarballylate

101. Cid_311

102. K-lyte/cl (salt/mix)

103. Citric Acid [mi]

104. K-lyte Ds (salt/mix)

105. Acidum Citricum Monohydrate

106. Bmse000076

107. Hoc(ch2cooh)2cooh

108. Ec 201-069-1

109. Citric Acid [fhfi]

110. Citric Acid [hsdb]

111. Ncistruc1_000057

112. Ncistruc2_000099

113. Nciopen2_004062

114. Nciopen2_004502

115. Oprea1_502996

116. Bspbio_003240

117. Citric Acid Anhydrous (jan)

118. 4-03-00-01272 (beilstein Handbook Reference)

119. Citric Acid, Anhydrous, Usp

120. Mls001066346

121. Citric Acid [who-dd]

122. Citric Acid (fragrance Grade)

123. Citric Acid, Anhydrous (usp)

124. Citricum Acidum [hpus]

125. Anhydrous Citric Acid (jp17)

126. Gtpl2478

127. Citric Acid (industrial Grade)

128. Citric Acid, Analytical Standard

129. Dtxsid3020332

130. Bdbm14672

131. Citric Acid, P.a., 99.5%

132. Kbio3_002740

133. 4o61

134. Citric Acid 5% Solution In Water

135. Citric Acid, Electrophoresis Grade

136. Hms1787n01

137. Hms2268b04

138. Pharmakon1600-01300013

139. Zinc895081

140. Anhydrous Citric Acid [ii]

141. Anhydrous Citric Acid [jan]

142. Citric Acid 10% Solution In Water

143. Hy-n1428

144. Str12052

145. Tox21_113436

146. Tox21_202405

147. Tox21_300124

148. Bbl002530

149. Nsc759606

150. S5761

151. Stk286098

152. Citric Acid,anhydrous [vandf]

153. Akos000119911

154. Anhydrous Citric Acid [mart.]

155. Citric Acid, Lr, Anhydrous, >=99%

156. 2-hydroxy-1,2,3-propanetricarboxylate

157. Acidum Citricum [who-ip Latin]

158. Cs-6965

159. Db04272

160. 3-carboxy-3-hydroxypentane-1,5-dioate

161. Citric Acid, >=99.5%, Fcc, Fg

162. Citric Acid, Acs Reagent, >=99.5%

163. Citric Acid, Anhydrous Powder, A.c.s.

164. 2-hydroxy-1,3-propanetricarboxylic Acid

165. Citric Acid, Anhydrous [who-ip]

166. Ncgc00090954-01

167. Ncgc00090954-02

168. Ncgc00090954-04

169. Ncgc00090954-05

170. Ncgc00254055-01

171. Ncgc00259954-01

172. 2-hydroxypropane-1,2,3-tricarboxylicacid

173. Bp-31028

174. Citric Acid, Anhydrous Granular, A.c.s.

175. Nci60_022579

176. Smr000471840

177. Citric Acid 50% Solution In Water (w/w)

178. Sbi-0206765.p001

179. Citric Acid, Saj First Grade, >=99.5%

180. 2-hydroxy-1,2,3-propane Tricarboxylic Acid

181. 2-hydroxy-1,2,3-propanenetricarboxylic Acid

182. Anhydrous Citric Acid [usp Monograph]

183. B7297

184. C1949

185. Citric Acid, Anhydrous [ep Impurity]

186. Citric Acid, Aqueous Solution (food Grade)

187. Citric Acid, Vetec(tm) Reagent Grade, 99%

188. Ft-0623957

189. Ft-0665073

190. Ft-0728530

191. Citric Acid, Anhydrous [usp Impurity]

192. Clenpiq Component Anhydrous Citric Acid

193. C00158

194. D00037

195. Ae-562/40806920

196. Anhydrous Citric Acid Component Of Clenpiq

197. Citric Acid, Bioultra, Anhydrous, >=99.5% (t)

198. Q159683

199. J-520099

200. 1,2,3-propanetricarboxylic Acid, 2-hydroxy- (9ci)

201. Z56754862

202. Citric Acid (monohydrate): H2o = 1 G : 1 Ml Solution

203. Citric Acid, Certified Reference Material, Tracecert(r)

204. Citric Acid, Meets Usp Testing Specifications, Anhydrous

205. F2191-0222

206. 8f5d336a-442d-434a-9fb0-e400ff74e343

207. Citrate Standard For Ic, 1000 Mg/l, Analytical Standard

208. 1,2,3-propanetricarboxylic Acid,2-hydroxy (citric Acid)

209. Citric Acid, United States Pharmacopeia (usp) Reference Standard

210. Citric Acid (constituent Of Cranberry Liquid Preparation) [dsc]

211. Citric Acid, Anhydrous, Cell Culture Tested, Plant Cell Culture Tested

212. Citric Acid, Anhydrous, European Pharmacopoeia (ep) Reference Standard

213. Citric Acid, Anhydrous, Free-flowing, Redi-dri(tm), Acs Reagent, >=99.5%

214. Citric Acid (constituent Of Garcinia Cambogia And Garcinia Indica) [dsc]

215. Citric Acid, Anhydrous, Pharmaceutical Secondary Standard; Certified Reference Material

216. Citric Acid, Meets Analytical Specification Of Ph. Eur., Bp, Usp, E330, Anhydrous, 99.5-100.5% (based On Anhydrous Substance)

2.4 Create Date
2004-09-16
3 Chemical and Physical Properties
Molecular Weight 192.12 g/mol
Molecular Formula C6H8O7
XLogP3-1.7
Hydrogen Bond Donor Count4
Hydrogen Bond Acceptor Count7
Rotatable Bond Count5
Exact Mass192.02700259 g/mol
Monoisotopic Mass192.02700259 g/mol
Topological Polar Surface Area132 Ų
Heavy Atom Count13
Formal Charge0
Complexity227
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

Mesh Heading: Anticoagulants, chelating Agents

National Library of Medicine, SIS; ChemIDplus Record for Citric acid (77-92-9). Available from, as of April 17, 2006: https://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp


/EXPL THER/ Regional citrate anticoagulation (RCA) is an effective form of anticoagulation for continuous renal replacement therapy (CRRT) in patients with contraindications to heparin. Its use has been very limited, possibly because of the need for special infusion solutions and difficult monitoring of the metabolic effects./The objective of this study was/ to investigate the safety and the feasibility of an RCA method for continuous veno-venous hemofiltration (CVVH) using commercially available replacement fluid. We evaluated 11 patients at high risk of bleeding, requiring CVVH. RCA was performed using commercially available replacement fluid solutions to maintain adequate acid-base balance. We adjusted the rate of citrate infusion to achieve a post-filter ionized calcium concentration [iCa] <0.4 mmol/L when blood flow was <250 mL/min, or <0.6 mmol/L when blood flow was >250 mL/min. When needed, we infused calcium gluconate to maintain systemic plasma [iCa] within the normal range. Twenty-nine filters ran for a total of 965.5 hr. Average filter life was 33.6+/-20.5 hr. Asymptomatic hypocalcemia was detected in 6.9% of all samples. No [iCa] values <0.9 mmol/L were observed. Hypercalcemia (1.39+/-0.05 mmol/L) occurred in 2.5% of all samples. /The authors/ observed hypernatremia (threshold 153 mmol/L) and alkalosis (threshold 7.51) in only 9.3% and 9.4% respectively of all samples, mostly concomitantly. No patient showed any signs of citrate toxicity. /They/ developed a protocol for RCA during CVVH using commercially available replacement fluid that proved safe, flexible and applicable in an Intensive Care Unit (ICU) setting.

PMID:17417764 Cubattoli L et al; Int J Artif Organs. 30 (3): 244-52 (2007)


It has ... been used to dissolve urinary bladder calculi, & as mild astringent.

Troy, D.B. (Ed); Remmington The Science and Practice of Pharmacy. 21 st Edition. Lippincott Williams & Williams, Philadelphia, PA 2005, p. 1085


Citrate ... of ... value in alleviation of chronic metabolic acidosis ... from chronic renal insufficiency or syndrome of renal tubular acidosis ... usually prescribed in form of sodium citrate and citric acid soln, USP ...

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 806


Potassium citrate, up to 10 g daily, has been used as a potassium supplement; the potassium and sodium salts have been used, in similar dosages, as mild diuretics in humans.

Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 5:768


4.2 Drug Warning

A study of abdominal pain and severity of other side effects attributed to Picolax, a combination of citric acid, magnesium oxide and sodium picosulfate, was conducted among 267 patients, 55 of whom had inflammatory bowel disease, all of whom were given a full single dose of Picolax as preparation for radiology or endoscopy. The frequency of increased abdominal pain and severe side effects after Picolax administration was similar in the patients with inflammatory bowel disease and the patients with other colonic disorders. None of the patients with iron deficiency in whom investigations had yielded negative results reported severe side effects; this was significantly different from the proportion reporting severe side effects among the patients with inflammatory bowel disease, the irritable bowel syndrome and diverticular disease. The increase in the mean number of stools/24 hr after Picolax was lower in the patients with inflammatory bowel disease than in the other diagnostic groups. On review 2-4 wk after examination none of the patients with inflammatory bowel disease reported deterioration in their symptoms.

McDonagh AJ et al; Br Med J 299: 776-7 (1989)


Following the occurrence of aluminum encephalopathy in four patients with chronic renal failure, 34 azotemic patients seen during the same year and five volunteers who took varying combinations of aluminum hydroxide and an alkalinizing citrate (Shohl's) solution were studied. It was found that the four encephalopathic cases were older than the 34 azotemic patients (68 years + or - 14 standard deviation, versus 50 + or - 13, p< 0.05), had a higher mean serum aluminum value (727 ug/l + or - 320 versus 92 + or - 73, p< 0.005), had taken more aluminum hydroxide (5 g/day + or - 0.9 versus 1.6 + or - 1.8, p< 0.01), and more Shohl's solution (64 ml/day + or - 19 versus 20 + or - 29, p< 0.01). In all 38 patients the serum aluminum values correlated directly with age (p=0.01), aluminum hydroxide (p=0.001) and concomitant citrate intake (p=0.004). In the five healthy volunteers the 24 hr urinary aluminum excretion increased from a baseline of 22 ug + or - 19 standard deviation to 167 + or - 109 (p=0.05) during aluminum hydroxide intake, rising to 580 + or - 267 (p=0.01) during the simultaneous intake of citrate and aluminum hydroxide. Corresponding serum aluminum values were 11 ug/l + or - 2 standard deviation, 44 + or - 34 (p= 0.1), and 98 + or - 58 (p<0.05). Thus citrate seems to enhance aluminum absorption and may cause encephalopathy in patients with chronic renal failure, especially the elderly.

PMID:2914409 Bakir AA et al; Clin Nephrol 31 (1): 40-4 (1989)


5 Pharmacology and Biochemistry
5.1 MeSH Pharmacological Classification

Anticoagulants

Agents that prevent BLOOD CLOTTING. (See all compounds classified as Anticoagulants.)


Calcium Chelating Agents

Substances that bind to and sequester CALCIUM ions. (See all compounds classified as Calcium Chelating Agents.)


5.2 FDA Pharmacological Classification
5.2.1 Active Moiety
ANHYDROUS CITRIC ACID
5.2.2 FDA UNII
XF417D3PSL
5.2.3 Pharmacological Classes
Anti-coagulant [EPC]; Calcium Chelating Activity [MoA]; Calculi Dissolution Agent [EPC]; Decreased Coagulation Factor Activity [PE]; Acidifying Activity [MoA]
5.3 ATC Code

A - Alimentary tract and metabolism

A09 - Digestives, incl. enzymes

A09A - Digestives, incl. enzymes

A09AB - Acid preparations

A09AB04 - Citric acid


5.4 Absorption, Distribution and Excretion

/A portion/ of the circulating (mainly metabolic but also ingested) citric acid is excreted in urine, with 24-hour urine reference values between 1.5 and 3.68 mmol, corresponding to 0.29-0.71 g citric acid excreted per person per day.

United Nations Environment Programme: OECD; Screening Information Data Sheets on Citric Acid (77-92-9) (January 1997). Available from, as of May 9, 2006: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html


5.5 Metabolism/Metabolites

Citric acid is a normal metabolite and an intermediate in cellular oxidative metabolism ... The acid is formed in the mitochondrion after condensation of acetate with oxaloacetate. The six-carbon acid is then successively degraded to a series of four-carbon acids, effectively accomplishing oxidation of acetate in the cell.

Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 5:767


In human (as well as in animal and plant) physiology, citric acid is a very common intermediate in one of the central biochemical cycles, the Krebs or tricarboxylic acid cycle, which takes place in every cell. It completes the breakdown of pyruvate formed from glucose through glycolysis, thereby liberating carbon dioxide and a further four hydrogen atoms which are picked up by electron transport molecules. Thus, in man approximately 2 kg of citric acid are formed and metabolised every day. This physiological pathway is very well developed and capable of processing very high amounts of citric acid as long as it occurs in low concentrations.

United Nations Environment Programme: OECD; Screening Information Data Sheets on Citric Acid (77-92-9) (January 2001). Available from, as of May 9, 2006: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html


Citric acid in reaction with enzyme citratase /citrate lyase/ yields oxaloacetic acid & acetic acid.

Fenaroli's Handbook of Flavor Ingredients. Volume 2. Edited, translated, and revised by T.E. Furia and N. Bellanca. 2nd ed. Cleveland: The Chemical Rubber Co., 1975., p. 785


5.6 Mechanism of Action

... The NK(2), and to a lesser extent the NK(1), receptors have been shown to be involved with citric acid-induced bronchoconstriction in the guinea pig, which is in part mediated by endogenously released bradykinin. Tachykinins and bradykinin could also modulate citric acid-induced bronchoconstriction. ... Bronchoconstriction induced by citric acid inhalation in the guinea pig, mainly caused by the tachykinin NK(2) receptor, is counteracted by bronchoprotective NO after activation of bradykinin B(2) and tachykinin NK(1) receptors in airway epithelium.

PMID:11749919 Ricciardolo FL; Am J Med 111 (Suppl 8A): 18S-24S (2001)


... A concentration of 47.6 mmol/L of citric acid (pH 2.3) in water led to total cell death within three minutes of incubation /with gingival fibroblasts (GF)/. Media containing 23.8 mmol/L and 47.6 mmol/L of citric acid exerted strong cytotoxicity (47 to 90 per cent of cell death) and inhibited protein synthesis (IC50 = 0.28 per cent) of GF within three hours of incubation. Incubation of cells in a medium containing 11.9 mmol/L of citric acid also suppressed the attachment and spreading of fibroblasts on culture plates and Type I collagen, with 58 per cent and 22 per cent of inhibition, respectively. Culture medium supplemented with 11.9, 23.8 and 47.6 mmol/L of citric acid also led to extracellular acidosis by decreasing the pH value from 7.5 to 6.3, 5.2 and 3.8, respectively.

PMID:10452169 Lan WC et al; Aust Dent J 44 (2): 123-30 (1999)


Inhalation of citric acid (CA) causes airway constriction and coughing. To investigate the role of mast cells in CA-induced airway constriction and cough, three experiments using guinea pigs were carried out. In the first experiment, /the authors/ used compound 48/80 to deplete mast cells, cromolyn sodium to stabilize mast cells, MK-886 to inhibit synthesis of leukotrienes, pyrilamine to antagonize histamine H1 receptor, methysergide to antagonize serotonin receptor, and indomethacin to inhibit cyclooxygenase. In the second experiment, compound 48/80-pretreated animals were divided into 2 parts; the first one was used to test the role of exogenous leukotriene (LT) C4, while the second one to test the role of exogenous histamine. Decreases in respiratory compliance (Crs) and forced expiratory volume in 0.1 sec (FEV0.1) were used as indicators for airway constriction in anesthetized guinea pigs. CA-induced cough was recorded for 12 min using a barometric body plethysmograph in conscious animals. In the third experiment, the activation of mast cells upon CA inhalation was investigated by determining lung tissue or arterial plasma histamine concentration in animals. Exposure to CA induced marked airway constriction and increase in cough number. Compound 48/80, cromolyn sodium, MK-886 and pyrilamine, but not indomethacin or methysergide, significantly attenuated CA-induced airway constriction and cough. Injection of LTC4 or histamine caused a significant increase in CA-induced airway constriction and cough in compound 48/80-pretreated animals. In addition, CA inhalation caused significant increase in lung tissue and plasma histamine concentrations, which were blocked by compound 48/80 pretreatment. These results suggest that mast cells play an important role in CA aerosol inhalation-induced airway constriction and cough via perhaps mediators including LTs and histamine.

PMID:20359123 Lai YL et al; Chin J Physiol. 52 (5 Suppl): 332-8 (2009)


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01-Jan-2021
31-Aug-2024
KGS
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Quantity (KGS) & Unit rate (USD/KGS) over time

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DOSAGE - SOLUTION;IRRIGATION - 6.602GM/100ML;...DOSAGE - SOLUTION;IRRIGATION - 6.602GM/100ML;198MG/100ML;3.177GM/100ML

USFDA APPLICATION NUMBER - 19481

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DOSAGE - FOR SOLUTION;ORAL - 12GM/PACKET;3.5G...DOSAGE - FOR SOLUTION;ORAL - 12GM/PACKET;3.5GM/PACKET;10MG/PACKET **Federal Register determination that product was not discontinued or withdrawn for safety or effectiveness reasons**

USFDA APPLICATION NUMBER - 202535

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DOSAGE - SOLUTION;ORAL - 12GM/BOT;3.5GM/BOT;1...DOSAGE - SOLUTION;ORAL - 12GM/BOT;3.5GM/BOT;10MG/BOT

USFDA APPLICATION NUMBER - 209589

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