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Chemistry

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Also known as: 71963-77-4, Artesaph, Falcidol, Gvither, Larither, Malartem
Molecular Formula
C16H26O5
Molecular Weight
298.37  g/mol
InChI Key
SXYIRMFQILZOAM-GXTLMGRASA-N
FDA UNII
C7D6T3H22J

Artemether
An artemisinin derivative that is used in the treatment of MALARIA.
Artemether is an Antimalarial.
1 2D Structure

Artemether

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
(4S,5R,8S,9R,10S,12R,13R)-10-methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane
2.1.2 InChI
InChI=1S/C16H26O5/c1-9-5-6-12-10(2)13(17-4)18-14-16(12)11(9)7-8-15(3,19-14)20-21-16/h9-14H,5-8H2,1-4H3/t9-,10-,11+,12+,13+,14-,15?,16-/m1/s1
2.1.3 InChI Key
SXYIRMFQILZOAM-GXTLMGRASA-N
2.1.4 Canonical SMILES
CC1CCC2C(C(OC3C24C1CCC(O3)(OO4)C)OC)C
2.1.5 Isomeric SMILES
C[C@@H]1CC[C@H]2[C@H]([C@H](O[C@H]3[C@@]24[C@H]1CCC(O3)(OO4)C)OC)C
2.2 Other Identifiers
2.2.1 UNII
C7D6T3H22J
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Alpha Artemether

2. Alpha-artemether

3. Artemether

4. Artemether, (3r-(3alpha,5abeta,6alpha,8abeta,9alpha,10beta,12beta,12ar*))-isomer

5. Artemether, (3r-(3alpha,5abeta,6beta,8aalpha,9alpha,10beta,12beta,12ar*))-isomer

6. Artemether, (3r-(3alpha,5abeta,6beta,8abeta,9alpha,10alpha,12beta,12ar*))-isomer

7. Artenam

8. Beta Arthemeter

9. Beta-arthemeter

10. O Methyldihydroartemisinine

11. O-methyldihydroartemisinine

2.3.2 Depositor-Supplied Synonyms

1. 71963-77-4

2. Artesaph

3. Falcidol

4. Gvither

5. Larither

6. Malartem

7. .beta.-artemether

8. Artemether [inn]

9. Artemether (sm-224)

10. C7d6t3h22j

11. Ss-artemether

12. Nsc-665970

13. Nsc-759820

14. Artemether [mi]

15. Artemether [jan]

16. Artemether [hsdb]

17. Artemether [usan]

18. (+)-artemether

19. Artemether [vandf]

20. Artemether [mart.]

21. Artemether [usp-rs]

22. Artemether [who-dd]

23. Artemether [who-ip]

24. Artemether [orange Book]

25. Schembl19967613

26. Coartem Component Artemether

27. (1r,4s,5r,8s,9r,10s,12r,13r)-10-methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane

28. (3r,5as,6r,8as,9r,10s,12r,12ar)-decahydro-10-methoxy-3,6,9-trimethyl-3,12-epoxy-12h-pyrano(4,3-j)-1,2-benzodioxepin

29. (3r,5as,6r,8as,9r,10s,12r,12ar)-decahydro-10-methoxy-3,6,9-trimethyl-3,12-epoxy-12h-pyrano[4,3-j]-1,2-benzodioxepin

30. 3,12-epoxy-12h-pyrano(4,3-j)-1,2-benzodioxepin, Decahydro-10-methoxy-3,6,9-trimethyl-, (3r,5as,6r,8as,9r,10s,12r,12ar)-

31. Artemetherum [who-ip Latin]

32. .beta.-dihydroartemisinin Methyl Ether

33. Akos016339568

34. Artemether Component Of Coartem

35. Ks-5314

36. Artemether 100 Microg/ml In Acetonitrile

37. As-11606

38. 963a774

39. (3r,5as,6r,8as,9r,10s,12r,12ar)-10-methoxy-3,6,9-trimethyldecahydro-3,12-epoxypyrano(4,3-j)-1,2-benzodioxepine

2.4 Create Date
2005-08-01
3 Chemical and Physical Properties
Molecular Weight 298.37 g/mol
Molecular Formula C16H26O5
XLogP33.1
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count5
Rotatable Bond Count1
Exact Mass298.17802393 g/mol
Monoisotopic Mass298.17802393 g/mol
Topological Polar Surface Area46.2 Ų
Heavy Atom Count21
Formal Charge0
Complexity429
Isotope Atom Count0
Defined Atom Stereocenter Count7
Undefined Atom Stereocenter Count1
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

MESH Heading: Antimalarial, antifungal, antiprotozoal, coccidiostats, schistosomicides

National Library of Medicine, SIS; ChemIDplus Record for Artemether (71963-77-4), MESH Heading. Available from, as of July 26, 2006: https://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp


Therap Cat: Antimalarial

O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 140


To counter the threat of resistance of P. falciparum to monotherapies, and to improve treatment outcome, combinations of antimalarials are now recommended by WHO for the treatment of falciparum malaria. ...The following ACTs are currently recommended: artemether-lumefantrine.

WHO; WHO Guidelines for the Treatment of Malaria (2006). Available from, as of July 31, 2006: https://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf


Artemether-lumefantrine: This is currently available as co-formulated tablets .... The total recommended treatment is a 6-dose regimen of artemether-lumefantrine twice a day for 3 days. An advantage of this combination is that lumefantrine is not available as a monotherapy and has never been used by itself for the treatment of malaria. Recent evidence indicates that the therapeutic response and safety profile in young children of less than 10 kg is similar to that in older children, and artemether-lumefantrine is now recommended for patients 5 kg. Lumefantrine absorption is enhanced by co-administration with fat. Low blood levels, with resultant treatment failure, could potentially result from inadequate fat intake, and so it is essential that patients or carers are informed of the need to take this ACT /antimalarial combination therapy/ with milk or fat-containing food -- particularly on the second and third days of treatment.

WHO; WHO Guidelines for the Treatment of Malaria (2006). Available from, as of July 31, 2006: https://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf


For more Therapeutic Uses (Complete) data for ARTEMETHER (11 total), please visit the HSDB record page.


4.2 Drug Warning

Transient first-degree heart block, dose-related reversible decreases in reticulocyte and neutrophil counts, and temporary elevations of serum aspartate aminotransferase activity have been reported ... Brief episodes of drug-induced fever in human volunteers were noted in some studies ... /Artemisinin drugs/

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1075


Because high doses of artemisinin drugs can produce neurotoxicity, prolongation of the QT interval, bone marrow depression, and fetal reabsorption in experimental animals, the possibility of long-term toxicity in human beings exists. /Artemisinin drugs/

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1075


Some patients cannot tolerate oral treatment, and will require parenteral or rectal administration for 1-2 days until they can swallow and retain oral medication reliably. Although such patients may not show signs of severity, they should receive the same antimalarial dose regimens as for severe malaria.

WHO; WHO Guidelines for the Treatment of Malaria (2006). Available from, as of July 31, 2006: https://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf


Some patients may have no signs of severity but on examination of the blood film are found to have very high parasitaemia. The risks associated with high parasitaemia vary depending on the age of the patient and on transmission intensity. Thus cut-off values and definitions of hyperparasitaemia also vary. Patients with high parasitaemias are at an increased risk of treatment failure and of developing severe malaria, and therefore have an increased risk of dying. These patients can be treated with the oral Antimalarial Combination Therapies (ACTs) recommended for uncomplicated malaria. However, they require close monitoring to ensure that the drugs are retained and that signs of severity do not develop, and they may require a longer course of treatment to ensure cure.

WHO; WHO Guidelines for the Treatment of Malaria (2006). Available from, as of July 31, 2006: https://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf


For more Drug Warnings (Complete) data for ARTEMETHER (18 total), please visit the HSDB record page.


5 Pharmacology and Biochemistry
5.1 MeSH Pharmacological Classification

Antimalarials

Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585) (See all compounds classified as Antimalarials.)


5.2 FDA Pharmacological Classification
5.2.1 Active Moiety
ARTEMETHER
5.2.2 FDA UNII
C7D6T3H22J
5.2.3 Pharmacological Classes
Established Pharmacologic Class [EPC] - Antimalarial
5.3 Absorption, Distribution and Excretion

Little or none of the administered drugs or dihydroartemisinin is recovered in urine. /Dihydroartemisinin/

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1072


After intramuscular administration pharmacokinetics indicated peak plasma levels of artemether (AM) at 2 to 4 hours post-dose, slow elimination and a tendency to accumulate after repeated administration. Only low levels of the major metabolite, dihydroartemisinin (DHA), were found. AM levels in the cerebrospinal fluid (CSF) were < 10% of plasma levels. After oral administration AM concentrations were considerably lower than after i.m. administration. The concentration of DHA was high on day 1 but almost nil on day 7 indicating its fast inactivation in dogs. Two hours after the 8th oral administration neither AM nor DHA was detected in CSF which may explain the absence of neurotoxicity in dogs after oral administration of AM.

PMID:10661809 Classen W et al; Exp Toxicol Pathol 51 (6): 507-16 (1999)


The pharmacokinetics of intramuscular artemether and its major plasma metabolite-dihydroartemisinin, were investigated in patients with severe manifestations of falciparum malaria. Six severe falciparum malaria patients with acute renal failure (ARF) and 11 without ARF were recruited into the study. They were treated with intramuscular artemether at a loading dose of 160 mg, followed by daily doses of 80 mg for another 6 days (total dose 640 mg). Patients with and without ARF showed a good initial response to treatment; the parasite and fever clearance times were 66 (30 to 164) and 76 (36 to 140) hr (median (range)), respectively. None had reappearance of parasitaemia in their peripheral blood smear within 7 days of initiation of treatment. In comatose patients, the time to recovery of consciousness was 51.6 (22 to 144) hr. Artemether was detected in plasma as early as 1hr after a 160 mg dose, and declined to undetectable levels within 24 hr in most cases. Patients with ARF had significantly higher Cmax (2.38 (1.89 to 3.95) vs 1.56 (1.05 to 3.38) ng/mL/mg dose), and lower Vz/F (5.45 (3.2 to 6.9) vs 8.6 (4.2 to 12.3) L/kg) and CL/F (7.4 (5.4 to 13.8) vs 19.1 (8.5 to 25.1) mL/min/kg) when compared to those without ARF. In addition, t1/2z, was significantly longer in ARF patients (7.0 (5.5 to 10.0) vs 5.7 (4.2 to 6.6) hr). The parmacokinetics of dihydroartemisinin in the two groups were comparable. ARF significantly modified the pharmacokinetics of intramuscular artemether. The changes could be contributed to either improved absorption/bioavailability, a reduction of systemic clearance, or a change in plasma protein binding of the drug.

PMID:9663816 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1873641 Karbwang J et al; Br J Clin Pharmacol 45: 597-600 (1998)


Dihydroartemisinin is rapidly absorbed following oral administration, reaching peak levels after around 2.5 hr. Absorption via the rectal route is somewhat slower, with peak levels occurring around 4 hr after administration. Plasma protein binding is around 55%. Elimination half-life is approximately 45 min via intestinal and hepatic glucuronidation. /Dihydroartemisinin/

WHO; WHO Guidelines for the Treatment of Malaria (2006). Available from, as of July 31, 2006: https://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf


For more Absorption, Distribution and Excretion (Complete) data for ARTEMETHER (6 total), please visit the HSDB record page.


5.4 Metabolism/Metabolites

Artemether ... /is/ converted to dihydroartemisinin ... The antimalarial effect of artemisinin compounds results primarily from dihydroartemisinin ...

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1072


Artemisinin is completely and rapidly absorbed after oral administration in rats. However, a very low plasma level was obtained even after a dose of 300 mg/kg. Liver was found to be the chief site of inactivation. When artemisinin was given i.m., significant and more persistent plasma levels were detected. Artemisinin was shown to pass the blood-brain and blood-placenta barriers after i.v. injection. Very little unchanged artemisinin was found in the urine or feces in 48 hours regardless of the route of administration. Metabolites identified after administration to humans include deoxyartemisinin, deoxydihydroartemisinin, and 9,10-dihydroxydeoxyartemisinin. /Artemisinin/

PMID:2084705 Lee IS, Hufford CD; Pharmacol Ther. 48 (3): 345-355 (1990)


5.5 Biological Half-Life

Artemether ... /is/ converted to dihydroartemisinin ... which rapidly disappears from plasma with a half-life of about 45 min.

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1072


5.6 Mechanism of Action

Artemether (AM) is an antimalarial drug derived from artemisinin (Qinghaosu), an extract of the herb Artemisia annua L., sweet wormwood. Its antiparasitic effect is that of a schizontocide and is explained by rapid uptake by parasitized erythrocytes and interaction with a component of hemoglobin degradation resulting in formation of free radicals. It has been shown to exhibit a high clinical cure rate.

PMID:10661809 Classen W et al; Exp Toxicol Pathol 51 (6): 507-16 (1999)


Two theories have been put forward for the mode of antimalarial action of the artemisinin antimalarials, in accodance with the known properties of peroxides with medicinal activity. The first assumes that the artemisinins must be activated by contact with either reduced haem (ferrous haem, Fe(ll)PPIX) or non-haem ferrous iron (exogenous iron), causing cleavage of the peroxide to generate oxygen-centered radicals (alkoxy radicals') which are then presumed to be converted into carbon-centered radicals by transfer of proximate hydrogen atoms from the periphery of the peroxide molecule. These carbon-centered radicals are then thought to alkylate sensitive, yet unspecified, biomolecules in the parasite. A second theory argues for a process in which the intact artemisinin binds to a site within a vital protein in the parasite. The act of binding causes the peroxide to be converted to hydroperoxide or similar open peroxide, which in accordance with known properties of such compounds, generates one or more active chemical entities, either oxidizing agents or oxygen transfer agents per se, or oxygen-centered free radicals. This would be associated with the binding process. In such a way, the artemisinins might act as (irreversibile) inhibitors. Iron may, or may not, be associated with the activation process. No specific biological target in the parasite has yet been identified in support of this theory, but it may be membrane-bound proteins.

WHO; Artesunate Rectal Capsules (2002). FDA Division of Anti-Infective Drug Products Advisory Committee Briefing Document. The World Health Organization, Geneva, Switzerland, 53 pp


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08-Jan-2021
29-Mar-2025
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ABOUT THIS PAGE

Looking for 71963-77-4 / Artemether API manufacturers, exporters & distributors?

Artemether manufacturers, exporters & distributors 1

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PharmaCompass offers a list of Artemether API manufacturers, exporters & distributors, which can be sorted by GMP, USDMF, JDMF, KDMF, CEP (COS), WC, Price,and more, enabling you to easily find the right Artemether manufacturer or Artemether supplier for your needs.

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PharmaCompass also assists you with knowing the Artemether API Price utilized in the formulation of products. Artemether API Price is not always fixed or binding as the Artemether Price is obtained through a variety of data sources. The Artemether Price can also vary due to multiple factors, including market conditions, regulatory modifications, or negotiated pricing deals.

API | Excipient name

Artemether

Synonyms

71963-77-4, Artesaph, Falcidol, Gvither, Larither, Malartem

Cas Number

71963-77-4

Unique Ingredient Identifier (UNII)

C7D6T3H22J

About Artemether

An artemisinin derivative that is used in the treatment of MALARIA.

71963-77-4 Manufacturers

A 71963-77-4 manufacturer is defined as any person or entity involved in the manufacture, preparation, processing, compounding or propagation of 71963-77-4, including repackagers and relabelers. The FDA regulates 71963-77-4 manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. 71963-77-4 API Manufacturers are required to adhere to Good Manufacturing Practices (GMP) to ensure that their products are consistently manufactured to meet established quality criteria.

click here to find a list of 71963-77-4 manufacturers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PhamaCompass.

71963-77-4 Suppliers

A 71963-77-4 supplier is an individual or a company that provides 71963-77-4 active pharmaceutical ingredient (API) or 71963-77-4 finished formulations upon request. The 71963-77-4 suppliers may include 71963-77-4 API manufacturers, exporters, distributors and traders.

click here to find a list of 71963-77-4 suppliers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PharmaCompass.

71963-77-4 USDMF

A 71963-77-4 DMF (Drug Master File) is a document detailing the whole manufacturing process of 71963-77-4 active pharmaceutical ingredient (API) in detail. Different forms of 71963-77-4 DMFs exist exist since differing nations have different regulations, such as 71963-77-4 USDMF, ASMF (EDMF), JDMF, CDMF, etc.

A 71963-77-4 DMF submitted to regulatory agencies in the US is known as a USDMF. 71963-77-4 USDMF includes data on 71963-77-4's chemical properties, information on the facilities and procedures used, and details about packaging and storage. The 71963-77-4 USDMF is kept confidential to protect the manufacturer’s intellectual property.

click here to find a list of 71963-77-4 suppliers with USDMF on PharmaCompass.

71963-77-4 JDMF

The Pharmaceuticals and Medical Devices Agency (PMDA) established the Japan Drug Master File (JDMF), also known as the Master File (MF), to permit Japanese and foreign manufacturers of drug substances, intermediates, excipients, raw materials, and packaging materials (‘Products’) to voluntarily register confidential information about the production and management of their products in Japan.

The 71963-77-4 Drug Master File in Japan (71963-77-4 JDMF) empowers 71963-77-4 API manufacturers to present comprehensive information (e.g., production methods, data, etc.) to the review authority, i.e., PMDA (Pharmaceuticals & Medical Devices Agency).

PMDA reviews the 71963-77-4 JDMF during the approval evaluation for pharmaceutical products. At the time of 71963-77-4 JDMF registration, PMDA checks if the format is accurate, if the necessary items have been included (application), and if data has been attached.

click here to find a list of 71963-77-4 suppliers with JDMF on PharmaCompass.

71963-77-4 WC

A 71963-77-4 written confirmation (71963-77-4 WC) is an official document issued by a regulatory agency to a 71963-77-4 manufacturer, verifying that the manufacturing facility of a 71963-77-4 active pharmaceutical ingredient (API) adheres to the Good Manufacturing Practices (GMP) regulations of the importing country. When exporting 71963-77-4 APIs or 71963-77-4 finished pharmaceutical products to another nation, regulatory agencies frequently require a 71963-77-4 WC (written confirmation) as part of the regulatory process.

click here to find a list of 71963-77-4 suppliers with Written Confirmation (WC) on PharmaCompass.

71963-77-4 NDC

National Drug Code is a comprehensive database maintained by the FDA that contains information on all drugs marketed in the US. This directory includes information about finished drug products, unfinished drug products, and compounded drug products, including those containing 71963-77-4 as an active pharmaceutical ingredient (API).

Finished drug products

The FDA updates the NDC directory daily. The NDC numbers for 71963-77-4 API and other APIs are published in this directory by the FDA.

Unfinished drugs

The NDC unfinished drugs database includes product listing information submitted for all unfinished drugs, such as active pharmaceutical ingredients (APIs), drugs intended for further processing and bulk drug substances for compounding.

Pharmaceutical companies that manufacture 71963-77-4 as an active pharmaceutical ingredient (API) must furnish the FDA with an updated record of all drugs that they produce, prepare, propagate, compound, or process for commercial distribution in the US at their facilities.

Compounded drug products

The NDC directory also contains data on finished compounded human drug products that contain 71963-77-4 and are produced by outsourcing facilities. While these outsourcing facilities are not mandated to assign a 71963-77-4 NDC to their finished compounded human drug products, they may choose to do so.

click here to find a list of 71963-77-4 suppliers with NDC on PharmaCompass.

71963-77-4 GMP

71963-77-4 Active pharmaceutical ingredient (API) is produced in GMP-certified manufacturing facility.

GMP stands for Good Manufacturing Practices, which is a system used in the pharmaceutical industry to make sure that goods are regularly produced and monitored in accordance with quality standards. The FDA’s current Good Manufacturing Practices requirements are referred to as cGMP or current GMP which indicates that the company follows the most recent GMP specifications. The World Health Organization (WHO) has its own set of GMP guidelines, called the WHO GMP. Different countries can also set their own guidelines for GMP like China (Chinese GMP) or the EU (EU GMP).

PharmaCompass offers a list of 71963-77-4 GMP manufacturers, exporters & distributors, which can be sorted by USDMF, JDMF, KDMF, CEP (COS), WC, API price, and more, enabling you to easily find the right 71963-77-4 GMP manufacturer or 71963-77-4 GMP API supplier for your needs.

71963-77-4 CoA

A 71963-77-4 CoA (Certificate of Analysis) is a formal document that attests to 71963-77-4's compliance with 71963-77-4 specifications and serves as a tool for batch-level quality control.

71963-77-4 CoA mostly includes findings from lab analyses of a specific batch. For each 71963-77-4 CoA document that a company creates, the USFDA specifies specific requirements, such as supplier information, material identification, transportation data, evidence of conformity and signature data.

71963-77-4 may be tested according to a variety of international standards, such as European Pharmacopoeia (71963-77-4 EP), 71963-77-4 JP (Japanese Pharmacopeia) and the US Pharmacopoeia (71963-77-4 USP).

Inform the supplier about your product requirements, specifying if you need a product with particular monograph like EP (Ph. Eur.), USP, JP, BP, or any other quality. In addition, clarify whether you need hydrochloride (HCl), anhydricum, base, micronisatum or a specific level of purity. To find reputable suppliers, utilize the filters and select those certified by GMP, FDA, or any other certification as per your requirement.
For your convenience, we have listed synonyms and CAS numbers to help you find the best supplier. The use of synonyms and CAS numbers can be helpful in identifying potential suppliers, but it is crucial to note that they might not always indicate the exact same product. It is important to confirm the product details with the supplier before making a purchase to ensure that it meets your requirements.
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