Absorption, Distribution and Excretion
The systemic exposure to mequinol was assessed in eight healthy subjects following two weeks of twice-daily topical treatment of a tretinoin and mequinol combination product. About dose of the product corresponding to about 37.3 ug/cm^2 of mequinol was applied to the subjects' backs. The mean Cmax for mequinol was 9.92 ng/mL (range between 4.22 and 23.62 ng/mL) and the Tmax was 2 hours (range between 1 to 2 hours). The safety of mequinol in this combination formulation is supported by the low systemic exposures of the agent in the subjects.
Mequinol is predominantly renally eliminated as its metabolites.
The volume of distribution is one that suggests mequinol is distributed throughout the total body water, and intracellular concentrations are not expected to vary greatly from gross measurements.
Readily accessible data regarding the clearance of mequinol is not available. The use of mequinol containing products is typically indicated for topical use.
Solage is a combination product composed of 2% mequinol (4-hydroxyanisole) and 0.01% tretinoin (all-trans-retinoic acid) in an ethanolic solution ... The purpose of this study was to evaluate the extent of percutaneous absorption of [(3)H]tretinoin and to estimate the systemic exposure to mequinol from this combination product when topically applied to the backs of healthy subjects. Eight subjects received bid /twice per day/ topical applications of nonradiolabelled 2% mequinol/0.01% tretinoin solution on a 400 sq cm area of the back for 14 days. The subjects then received a single topical application of 2% mequinol/0.01% ((3)H)tretinoin solution. After 12 hr, the radiolabelled dose was removed and bid /twice per day/ treatment with nonradiolabelled 2% mequinol/0.01% tretinoin solution was continued for 7 days. Plasma, urine and faecal samples were analysed for total radioactivity and plasma was analysed for both mequinol and tretinoin by GC/MS procedure. Mean percutaneous absorption of [(3)H]tretinoin based on the cumulative recoveries of radioactivity in the urine and faeces was about 4.5% (median 2.18%). Tretinoin concentrations in plasma did not increase above endogenous levels. This was consistent with the concentrations of radioactivity in plasma, which showed an average Cmax of 91 pg-eq/mL (median 26 ng/mL). Average Cmax and AUC(0-12 hr) values for mequinol were 10 ng/mL and 33 ng h/mL, respectively. Based on the results of this study, systemic toxicity from topical application of tretinoin in this formulation is unlikely, because percutaneous absorption of tretinoin is minimal and because endogenous levels of tretinoin are not increased following bid /twice per day/ dosing with this combination formulation. The safety of mequinol in this combination formulation is supported by the low systemic exposures of the subjects in this study compared with the systemic exposures at the highest doses in the dermal toxicity studies in mice (16.6-fold) and rats (34.6-fold).
In one study in healthy individuals, following topical application of 0.8 mL of the combination preparation containing mequinol 2% and tretinoin 0.01% on a 400-sq cm back skin area twice daily for 14 days, approximately 4.5% of a radiolabeled dose was recovered as tretinoin in urine and feces. In this study, plasma tretinoin concentrations did not increase above endogenous plasma concentrations and average peak plasma mequinol concentrations were about 10 ng/mL. /Solage/
There is also indication ... that the material was absorbed in toxic amounts when in solution, especially through abraded skin.

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Metabolism / Metabolites
Urine samples from melanoma patients treated with mequinol were analyzed and various mequinol metabolites were identified, including 3,4-dihydroxyanisole, the two o-methyl derivatives 3-hydroxy-4-methoxyanisole and 4-hydroxy-3-methoxyanisole, and even hydroquinone which may have originated at least partly from mequinol. All these identified metabolites were excreted predominantly as sulphates and glucuronides - only a small portion of the substances were present in urine in an unconjugated form. Ultimately, the 3,4-dihydroxyanisole is considered the most important metabolite of mequinol.
A tyrosinase-directed therapeutic approach for treating malignant melanoma uses depigmenting phenolic prodrugs such as 4-hydroxyanisole (4-HA) for oxidation by melanoma tyrosinase to form cytotoxic o-quinones. However, in a recent clinical trial, both renal and hepatic toxicity were reported as side effects of 4-HA therapy. In the following, 4-HA (200 mg/kg i.p.) administered to mice caused a 7-fold increase in plasma transaminase toxicity, an indication of liver toxicity. Furthermore, 4-HA induced-cytotoxicity toward isolated hepatocytes was preceded by glutathione (GSH) depletion, which was prevented by cytochrome p450 inhibitors that also partly prevented cytotoxicity. The 4-HA metabolite formed by NADPH/microsomes and GSH was identified as a hydroquinone mono-glutathione conjugate. GSH-depleted hepatocytes were much more prone to cytotoxicity induced by 4-HA or its reactive metabolite hydroquinone (HQ). Dicumarol (an NAD(P)H/quinone oxidoreductase inhibitor) also potentiated 4-HA- or HQ-induced toxicity whereas sorbitol, an NADH-generating nutrient, prevented the cytotoxicity. Ethylenediamine (an o-quinone trap) did not prevent 4-HA-induced cytotoxicity, which suggests that the cytotoxicity was not caused by o-quinone as a result of 4-HA ring hydroxylation. Deferoxamine and the antioxidant pyrogallol/4-hydroxy-2,2,6,6-tetramethylpiperidene-1-oxyl (TEMPOL) did not prevent 4-HA-induced cytotoxicity, therefore excluding oxidative stress as a cytotoxic mechanism for 4-HA. A negligible amount of formaldehyde was formed when 4-HA was incubated with rat microsomal/NADPH. These results suggest that the 4-HA cytotoxic mechanism involves alkylation of cellular proteins by 4-HA epoxide or p-quinone rather than involving oxidative stress.
Many of the well-known depigmenting agents such as hydroquinone and 4-hydroxyanisole are, in fact, melanocytotoxic chemicals which are oxidized in melanocytes to produce highly toxic compounds such as quinones. These cytotoxic compounds are responsible for the destruction of pigment cells, which results in skin depigmentation. However, cells are capable of protecting themselves against cytotoxic agents by intracellular glutathione (GSH). This protection takes place under the enzymatic action of the detoxification enzyme glutathione S-transferase (GST), which is responsible for the conjugation of toxic species to GSH. The depigmenting effect of hydroquinone is shown to be potentiated by buthionine sulfoximine (BSO) and cystamine as the result of the reduction of intracellular levels of GSH by these two agents. Additionally, BSO and cystamine are shown to inhibit the activity of GST. The combination of all-trans-retinoic acid (tretinoin, TRA) with hydroquinone or 4-hydroxyanisole is also known to produce synergetic skin depigmentation. TRA serves as a potent inhibitor of mammalian GSTs and is known to make cells more susceptible to the cytotoxic effect of chemicals by inhibiting the activity of this enzyme. This agent is also shown to reduce the level of intracellular GSH in certain cells. We have proposed that the mechanism of action of TRA to synergistically enhance the melanocytotoxic effect of chemicals involves the inhibition of GST and the impairment of glutathione-dependent cytoprotection against melanocytotoxic agents.
Yields 1,4-dimethoxybenzene in guinea pig, rat, rabbit, mouse. Yields 4-methoxycatechol, p-methoxyphenyl-beta-d-glucuronide, & p-methoxyphenyl sulfate in rabbit. /From Table/
4-Methoxyphenol has known human metabolites that include (2S,3S,4S,5R)-3,4,5-Trihydroxy-6-(4-methoxyphenoxy)oxane-2-carboxylic acid.

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Biological Half-Life
Mequinol demonstrated an elimination half-life of 30 to 90 minutes following intravenous infusion of 5 or 10 grams/m^2 over 3 to 5 hours in melanoma patients; similar values were reported after intra-arterial infusion.

Toxicity Summary
IDENTIFICATION AND USE: 4-Methoxyphenol (4-MP) is available as a colorless to white, waxy solid or white to tan, flaky, crystalline substance with the odor of caramel and phenol. It is used as an inhibitor for acrylic monomers and acrylonitirles, as a stabilizer for chlorinated hydrocarbons and ethyl cellulose, as an ultraviolet inhibitor, as a chemical intermediate in the manufacture of antioxidants, pharmaceuticals, plasticizers, and dyestuffs. It is also used as a medication for dyschromias, especially hyperpigmentation often in combination with Tretinoin (Solage). HUMAN EXPOSURE AND TOXICITY: In 11 of the 16 patients (69%; 95% confidence interval [CI], 41%-89%) total depigmentation was achieved using the 4-MP cream. Onset of depigmentation was between 4 and 12 months. Mild burning or itching was reported with the cream in 4 cases (25%). Of the 11 patients who responded to the 4-MP cream, 4 had recurrence of pigmentation (relapse rate of 36%; 95% CI, 11%-69%) after a treatment-free period of 2 to 36 months. Excessive application of 4-MP, can result in marked redness, peeling, discomfort, or hypopigmentation. Oral ingestion of the drug may lead to the same adverse effects as those associated with excessive oral intake of vitamin A (hypervitaminosis A). In a vinylidene chloride plant 2 out of 8 process workers handling hydroquinone monomethyl ether developed depigmentation (occupational leukoderma) of skin of forearms and in 1 of them depigmentation of skin of forehead. Report of the follow-up of 2 cases of leukodermia (vitiligo) following exposure to 4-MP described 8 years previously and survey of 169 men exposed to 4-MP or paratertiary-amyl-phenol or both revealed that repigmentation of a significant degree was found in one man and of a limited degree in the other. Screening by means of the Wood's light technique (an ultra-violet light which is absorbed by normally pigmented skin and reflected by non-pigmented skin) of the 169 men surveyed in the same plant revealed no cases of leukoderma attributed to exposure to 4-MP in 148 men tested or in the 129 men exposed to paratertiary-amyl-phenol. In regards to possible genotoxicity, results from cytogenetic analysis show that the salt of 4-MP (p-methoxyphenol phosphate) induced the decrease of numerical and structural chromosome aberration after the first passage of the treated cells. In terms of the results obtained by cytogenetic analysis the reduction of genetic instability seems to remain constant from the first to the sixth passage in the cell cultures treated with p-methoxyphenol phosphate associated to benzo(a)pyrene. ANIMAL STUDIES: Rabbit studies with 4-MP have shown that it can cause considerable necrosis if exposure is not limited to 1 day. Prolonged contact can cause a severe burn. There is also indication that the material is absorbed in toxic amounts when in solution, especially through abraded skin. Acute parenteral poisoning in rabbits included paralysis and anoxia at lower doses and CNS depression at high doses. 4-MP caused depigmentation of the skin when applied topically to guinea pigs (within 5 to 10 days of treatment) and miniature pigs. In a dermal teratology study in rabbits, there were no statistically significant differences in fetal malformation data; however marked hydrocephaly with visible doming of the head was observed in one mid-dose litter (12 and 0.06 mg/kg or 132 and 0.66 mg/sq m of 4-MP and tretinoin, respectively. 4-MP does not appear to be carcinogenic when applied topically. In studies with 5% or 10% 4-MP (0.02 mL) twice a week between the shoulder blades of mice (for 93 weeks) or interior ears of rabbits, there was no significant decrease in survival rates, or tumor incidence compared to controls. Tumors were evident when 4-MP was administered in the diet of F344 rats (30 male and 30 females) administered diets of 2% 4-MP for 104 weeks. Histopathological findings in the 4-MP case included atypical hyperplasias (male, 67%, female, 37%), papillomas (50%, 23%) and squamous-cell carcinomas (77%, 20%) in the forestomach. 4-MC induced forestomach papillomas (70%, 93%) and squamous-cell carcinomas (53%, 37%), also glandular stomach submucosal hyperplasias (90%, 93%), adenomas (100%, 100%) and adenocarcinomas (57%, 47%), with ulceration or erosion. No genotoxic effects were observed when 4-MP was tested in Salmonella typhimurium TA98, TA100, TA1535, and TA1537 or in rats exposed dermally for 6 months.

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Protein Binding
Readily accessible data regarding the protein binding of mequinol is not available.

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Interactions
Tests were carried out in cultured Chinese hamster ovary (CHO) cells (line CHO-AA8-4) and in X-irradiated Syrian hamster embryo cells (SHE) to investigate the effects of butylated-hydroxyanisole (BHA) on the metabolism and mutagenic activity of benzo(a)pyrene (BaP) and to compare them with those induced by butylated-hydroxytoluene (BHT) and p-methoxyphenol (PMO). Feeder Syrian hamster embryo cells were cocultured with target Chinese hamster ovary cells to provide metabolic transformation of benzo(a)pyrene. The mutagenicity of benzo(a)pyrene in target Chinese hamster ovary cells was reduced by up to 60% by pretreatment with p-methoxyphenol, butylated-hydroxyanisole, or butylated-hydroxytoluene. In Syrian hamster ovary cells, the antioxidants tested inhibited metabolism with reduction in levels of water soluble benzo(a)pyrene glucuronide conjugates in the extracellular medium and apparent increase in levels of intracellular monophenols. As a result of the antioxidant inhibited formation of reactive, electrophilic benzo(a)pyrene metabolites, there was reduction in the binding of benzo(a)pyrene to nuclear macromolecules, especially to DNA.
The modifying effects of para-methoxyphenol second stage treatment on N-methyl-N'-nitro-N-nitrosoguanidine initiated rat forestomach carcinogenesis were investigated. Groups of 15 6 week old male F344 rats were given a single intragastric administration of 150 mg/kg body wt N-methyl-N'-nitro-N-nitrosoguanidine and starting 1 week later were administered powdered diet containing 2.0, 1.0, 0.5, 0.25 or 0% para-methoxyphenol until week 52. para-methoxyphenol caused epithelial damage and hyperplasia in a dose-dependent manner in the forestomach epithelium but nevertheless was not associated with any increase in the incidence of either papillomas or squamous cell carcinomas. Stimulation of cell proliferation does not necessarily correlate with promotion in the second stage of two-stage forestomach carcinogenesis.
The modifying effects of five phenolic antioxidants on N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-initlated forestomach and glandular stomach carcinogenesis were investigated in male F344 rats. Groups of 20 rats were given an intragastric dose of 150 mg/kg body weight N-methyl-N-nitro-N-nitrosoguanine and starting from 1 week later received diet supplemented with 0.8% catechol, 1.0% 2-tert-butyl-4-methylphenol, 1.5% p-tert-butylphenol, 1.5% methylhydroquinone, 1.5% 4-methoxyphenol, or basal diet alone for 51 wk. Further groups of 10-15 rats were maintained as controls without prior treatment with N-methyl-N-nitro-N-nitrosoguanine. The incidences of squamous cell carcinoma of the forestomach in N-methyl-N-nitro-N-nitrosoguanine-treated animals were significantly elevated by the diets containlng catechol (P less than 0.001), 2-tert-butyl-4-methylphenol (P less than 0.001), or p-tert-butylphenol (P less than 0.01), while the development of carcinoma in situ was inhibited by 4-methoxyphenol (P less than 0.01). Treatment with catechol, 2-tert-butyl-4-methylphenol, p-tert-butylphenol, or 4-methoxyphenol alone induced forestomach hyperplasia at incidences of 86.7, 40, 93.3, and 100%, respectively. In the pyloric region of the glandular stomach, the development of adenomatous hyperplasia and adenocarcinoma after N-methyl-N-nitro-N-nitrosoguanine treatment was significantly enhanced by diet containing catechol (P less than 0.001). Moreover, treatment with catechol alone induced 100% adenomatous hyperplasia and induced adenocarcinoma in 20% of animals. ... While antioxidants causing proliferation in forestomach epithelium can markedly enhance carcinogenesis in this tissue, others displaying the same or greater potential for generating a hyperplastic response, like 4-methoxyphenol can exert an inhibitory effect. In addition, it was shown that catechol is an unequivocal glandular stomach carcinogen also possessing strong enhancing activity for N-methyl-N-nitro-N-nitrosoguanine-induced lesion development.
The chemopreventive effect of 40 and 80% maximum tolerated dose (MTD) levels of ascorbylpalmitate (AP), carbenoxolone (CBX), dimethylfumarate (DMF) and p-methoxyphenol (p-MP) administrated in the diet before and during initiation and postinitiation phases of azoxymethane (AOM)-induced colon carcinogenesis was studied in male F344 rats. The MTD levels of AP, CBX, DMF and p-MP were determined in male F344 rats and found to be 5000, 1500, 1000 and 1000 ppm, respectively, in modified AIN-76A diet. Based on these MTD values, 40 and 80% MTD levels of each agent was tested for their efficacy in colon carcinogenesis. At 5 weeks of age, groups of animals were fed the control (modified AIN-76A diet or diets containing 40 and 80% MTD levels of each AP, CBX, DMF and p-MP. At 7 weeks of age, all animals, except those in the vehicle (normal saline) treated groups, were given two weekly s.c. injections of AOM at a dose rate of 15 mg/kg body weight/week. All groups were continued on their respective dietary regimen until the termination of the experiment 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. The results indicate that dietary administration of 40% MTD of AP significantly inhibited multiplicities (tumor/animal) of noninvasive and total (invasive plus noninvasive) adenocarcinoma of the colon (P < 0.05) and 80% MTD of AP significantly inhibited the incidence (% animals with tumors) and the multiplicities of invasive and total adenocarcinomas of the colon (P < 0.01). Dietary CBX at 40 and 80% MTD levels suppressed the incidence and multiplicities of invasive and total adenocarcinomas (P < 0.05 to 0.001) whereas 40 and 80% MTD of DMF and p-MP had significantly inhibited invasive adenocarcinoma incidence and multiplicity (P < 0.05 to 0.001). However, DMF and p-MP had no significant effect on noninvasive and total adenocarcinoma incidence and multiplicity (P > 0.05). These results suggest that AP and CBX possess potential chemopreventive properties against colon cancer.
For more Interactions (Complete) data for 4-METHOXYPHENOL (11 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 1600 mg/kg
LD50 Mouse ip 250 mg/kg
LD50 Rabbit ip 720-790 mg/kg

[1]. Postinflammatory hyperpigmentation: etiologic and therapeutic considerations. Am J Clin Dermatol. 2011 Apr 1;12(2):87-99.

[2]. Carcinogenicity of antioxidants BHA, caffeic acid, sesamol, 4-methoxyphenol and catechol at low doses, either alone or in combination, and modulation of their effects in a rat medium-term multi-organ carcinogenesis model. Carcinogenesis. 1998 Jan;19(1):207-12.

[3]. Increase in the levels of chaperone proteins by exposure to beta-estradiol, bisphenol A and 4-methoxyphenol in human cells transfected with estrogen receptor alpha cDNA. Toxicol In Vitro. 2009 Jun;23(4):728-35.

Therapeutic Uses
Antineoplastic Agents; Antioxidants
Dyschromias, in particular hyperpigmentation, are major issues of concern for people of color. Pigmentary disorders such as melasma and postinflammatory hyperpigmentation (PIH) can cause psychological and emotional distress and can pose a negative impact on a person's health-related quality of life. The precise etiology of these conditions is unknown. Therapies for melasma and PIH target various points during the cycle of melanin production and degradation. Therapies for these conditions include topical agents and resurfacing procedures. Hydroquinone remains the gold standard of topical agents. Other efficacious agents include kojic acid, azelaic acid, mequinol, and retinoids. Cosmeceutical agents include licorice, arbutin, soy, N-acetyl glucosamine, and niacinamide. Resurfacing procedures that have been used to treat melasma and PIH include chemical peels, microdermabrasion, lasers, and intense pulsed light. These procedures are best used in combination with topical bleaching agents. Given the propensity of darker skin to hyperpigment, resurfacing procedures should be used with care and caution. Maximal results are best achieved with repetitive, superficial, resurfacing modalities. In addition, ultraviolet protective measures such as broad-spectrum sunscreens are fundamental to the successful management of these conditions.
Postinflammatory hyperpigmentation (PIH) is a reactive hypermelanosis and sequela of a variety of inflammatory skin conditions. PIH can have a negative impact on a patient's quality of life, particularly for darker-skinned patients. Studies show that dyschromias, including PIH, are one of the most common presenting complaints of darker-skinned racial ethnic groups when visiting a dermatologist. This is likely due to an increased production or deposition of melanin into the epidermis or dermis by labile melanocytes. A variety of endogenous or exogenous inflammatory conditions can culminate in PIH and typically most epidermal lesions will appear tan, brown, or dark brown while dermal hypermelanosis has a blue-gray discoloration. Depigmenting agents target different steps in the production of melanin, most commonly inhibiting tyrosinase. These agents include hydroquinone, azelaic acid, kojic acid, arbutin, and certain licorice (glycyrrhiza) extracts. Other agents include retinoids, mequinol, ascorbic acid (vitamin C), niacinamide, N-acetyl glucosamine, and soy, and these products depigment by different mechanisms. Certain procedures can also be effective in the treatment of PIH including chemical peeling and laser therapy. It is important to note that these same therapeutic modalities may also play a role in causing PIH. Lastly, those lesions that are not amenable to medical or surgical therapy may experience some improvement with cosmetic camouflage.
Neither the safety nor effectiveness of Solage Solution for the prevention or treatment of melasma or postinflammatory hyperpigmentation has been established. /Included in US product label/ /Solage/
For more Therapeutic Uses (Complete) data for 4-METHOXYPHENOL (9 total), please visit the HSDB record page.

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Drug Warnings
Known hypersensitivity to mequinol or tretinoin or any ingredient in the formulation. /Solage/
Mequinol and tretinoin should be used with extreme caution in patients with eczema, since tretinoin may produce severe irritation of eczematous skin. In addition, mequinol and tretinoin is a dermal irritant and the risk of long-term sequelae from continued skin irritation for longer than 52 weeks is not known. Irritation of the skin induced by the drug may result in increased reactivity to environmental (eg, wind and cold exposure) stimuli. If local irritation becomes severe, temporary or permanent discontinuance of the drug or dosage reduction should be considered. /Solage/
Safety and efficacy of mequinol and tretinoin have not been established in patients with moderately or heavily pigmented skin. /Solage/
Patients with a personal or family history of vitiligo may experience enhanced response to mequinol and tretinoin topical solution. During clinical trials, one patient with a family history of vitiligo experienced hypopigmentation in areas not treated with the drug and some areas continued to worsen for at least 1 month after discontinuance of therapy; hypopigmentation became mild after 6 weeks and resolved in some, but not all, lesions by day 106 post-treatment. /Solage/
For more Drug Warnings (Complete) data for 4-METHOXYPHENOL (13 total), please visit the HSDB record page.

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Pharmacodynamics
Mequinol is in fact considered a melanocytotoxic chemical which when oxidized in melanocytes results in the formation of toxic entities like quinones. Such cytotoxic compounds subsequently have the potential to damage and destroy pigment cells, therefore causing skin depigmentation. In response, skin cells are naturally capable of protecting themselves against such cytotoxic agents with the help of endogenous intracellular glutathione and the detoxification action of glutathione S-transferase on the cytotoxic compounds. Regardless, it is consequently by way of this seemingly negative and damaging pharmacodynamic profile by which the mechanism of action of mequinol is sometimes described.

C7H8O2

124.1372

124.052

150-76-5

Mequinol-d4;126840-02-6

9015

White to light brown solid powder

1.1±0.1 g/cm3

243.0±0.0 °C at 760 mmHg

56 °C

120.8±4.8 °C

0.0±0.5 mmHg at 25°C

1.535

1.31

1

2

1

9

75

0

NWVVVBRKAWDGAB-UHFFFAOYSA-N

InChI=1S/C7H8O2/c1-9-7-4-2-6(8)3-5-7/h2-5,8H,1H3

4-methoxyphenol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ≥ 100 mg/mL (~805.54 mM)
DMSO : ≥ 100 mg/mL (~805.54 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (20.14 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (20.14 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (20.14 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)