Vitamin Retinyl palmitate

D. Hartmann, D. Gysel, U. C. Dnbach, and I. Forgo, Pharmacokinetic modehng of the plasma concentration-time profile of the vitamin retinyl palmitate following mtramns-cular administration. Biopharm Drug Dispos 11 689-700 (1990). 

Fig. 1. Vitamin A and derivatives retinol (1), retinyl acetate [127-47-9] (2), retinyl palmitate [79-81-2] (3), and retinyl propionate [7069-42-3] (4).

Spectroscopic methods such as uv and fluorescence have rehed on the polyene chromophore of vitamin A as a basis for analysis. Indirectly, the classical Carr-Price colorimetric test also exploits this feature and measures the amount of a transient blue complex at 620 nm which is formed when vitamin A is dehydrated in the presence of Lewis acids. For uv measurements of retinol, retinyl acetate, and retinyl palmitate, analysis is done at 325 nm. More sensitive measurements can be obtained by fluorescence. Excitation is done at 325 nm and emission at 470 nm. Although useful, all of these methods suffer from the fact that the method is not specific and any compound which has spectral characteristics similar to vitamin A will assay like the vitamin... 

Retinal (Vitamin A aldehyde). Retinoic acid (Vitamin A acid), Retinyl acetate, Retinyl palmitate see entries in Chapter 4. 

The overall metabolism of vitamin A in the body is regulated by esterases. Dietary retinyl esters are hydrolyzed enzymatically in the intestinal lumen, and free retinol enters the enterocyte, where it is re-esterified. The resulting esters are then packed into chylomicrons delivered via the lymphatic system to the liver, where they are again hydrolyzed and re-esterified for storage. Prior to mobilization from the liver, the retinyl esters are hydrolyzed, and free retinol is complexed with the retinol-binding protein for secretion from the liver [101]. Different esterases are involved in this sequence. Hydrolysis of dietary retinyl esters in the lumen is catalyzed by pancreatic sterol esterase (steryl-ester acylhydrolase, cholesterol esterase, EC 3.1.1.13) [102], A bile salt independent retinyl-palmitate esterase (EC 3.1.1.21) located in the liver cell plasma hydrolyzes retinyl esters delivered to the liver by chylomicrons. Another neutral retinyl ester hydrolase has been found in the nuclear and cytosolic fractions of liver homogenates. This enzyme is stimulated by bile salts and has properties nearly identical to those observed for... 

J. Boehnlein, A. Sakr, J. L. Lichtin, R. L. Bronaugh, Characterization of Esterase and Alcohol Dehydrogenase Activity in Skin. Metabolism of Retinyl Palmitate to Retinol (Vitamin A) During Percutaneous Absorption , Pharm. Res. 1994, 11, 1155-1159. 

Biesalski, H. K., Reifen, R., Ftirst, P., and Edris, M. (1999). Retinyl palmitate supplementation by inhalation of an aerosol improves vitamin A status of preschool children in Gondar (Ethiopia). Br.. Nutr. 82,179-182. 

Sobeck, U., Fischer, A., and Biesalski, H. K. (2003). Uptake of vitamin A in buccal mucosal cells after topical application of retinyl palmitate A randomised, placebo-controlled and double-blind trial. Br. J. Nutr. 90, 69-74. 

In the body retinol can also be made from the vitamin precursor carotene. Vegetables like carrots, broccoli, spinach and sweet potatoes are rich sources of carotene. Conversion to retinol can take place in the intestine after which retinyl esters are formed by esterifying retinol to long chain fats. These are then absorbed into chylomicrons. Some of the absorbed vitamin A is transported by chylomicrons to extra-hepatic tissues but most goes to the liver where the vitamin is stored as retinyl palmitate in stellate cells. Vitamin A is released from the liver coupled to the retinol-binding protein in plasma. 

Some conversion into the anhydrovitamin (112) occurs during silica gel t.l.c. of retinyl palmitate in non-polar solvents. Some new colour reactions of vitamin A are reported to be better than the Carr-Price reaction. The kinetics and mechanism of acid-catalysed isomerization of retinyl acetate into the trans-retro-derivative (113) have been studied. Oppenauer oxidation of kitol (39) results in specific cyclopentanol-cyclopentanone oxidation. ... 

As vitamin A and carotene are in the fat portion of milk, the vitamin A activity is removed with the milk fat during separation into cream and lowfat and skim milks. Consequently, standards of identity established by the U.S. Food and Drug Administration (FDA) mandate the addition of vitamin A (e.g., retinyl palmitate) to fluid lowfat and skim milks and to nonfat dry milk to a level approximating that found in whole milk from cows on summer pasture. That is, at least 2000 IU of vitamin A must be present in each quart of lowfat and skim milk (FDA... 

Foods are supplemented with vitamin A in the form of standardized preparations of synthetic fatty acyl esters, nowadays chiefly retinyl palmitate. The preparations are available commercially as either dilutions in high-quality vegetable oils containing added vitamin E as an antioxidant or as dry, stabilized beadlets in which the vitamin A is dispersed in a solid matrix of gelatin and sucrose or gum acacia and sucrose. The oily preparations are used to supplement fat-based foods such as margarines the dry preparations are used in dried food products such as milk powder, infant formulas, and dietetic foods (24). 

Enzymatic hydrolysis is a nondestructive alternative to saponification for removing triglycerides in vitamin K determinations. For the simultaneous determination of vitamins A, D, E, and K in milk- and soy-based infant formulas and dairy products fortified with these vitamins (81), an amount of sample containing approximately 3.5-4.0 g of fat was digested for 1 h with lipase at 37°C and at pH 7.7. This treatment effectively hydrolyzed the glycerides, but only partially converted retinyl palmitate and a-tocopheryl acetate to their alcohol forms vitamin D and phyllo-quinone were unaffected. The hydrolysate was made alkaline in order to precipitate the fatty acids as soaps and then diluted with ethanol and extracted with pentane. A final water wash yielded an organic phase containing primarily the fat-soluble vitamins and cholesterol. 

Fig. 7 Comparative HPLC separations of a standard solution of six vitamins using (A) 250 X 4.0-mm-ID standard-bore and (B) 250 X 2.0-mm-ID narrow-bore columns. Stationary phase (both columns), 5-/tm Nu-cleosil-120-5 C8 (octyl) mobile phase, methanol/water (92 8). Flow rate (A) 0.7 ml/min, (B) 0.2 ml/min. Injection volume, 1 fi 1. Wavelength-programmed absorbance detection. Peaks (1) retinol (2) retinyl acetate (3) vitamin D3 (4) a-tocopherol (5) a-tocopheryl acetate (6) retinyl palmitate. (From Ref. 108.)...

Schneiderman et al. (90) extracted retinyl palmitate from commercial breakfast cereals using supercritical C02 and determined the vitamin by means of reversed-phase HPLC and electrochemical detection. Chromatograms of an unfortified wheat sample and a fortified bran-based cereal product are shown in Fig. 10. 

Fig. 10 HPLC chromatograms of supercritical fluid extracts of (A) an unfortified wheat sample and (B) a vitamin A-fortified bran-based ready-to-eat breakfast cereal. Column, 5-/rm Altex C8 (octyl) (150 X 4.6-mm ID) mobile phase, acetonitrile/2-propanol/aqueous 25 mM sodium perchlorate (45 45 10), 2.0 ml/min amperometric detection (oxidative mode), glassy carbon electrode, +1.2 V, vs saturated calomel electrode. Peak (1) retinyl palmitate. (Reprinted from Ref. 90, Copyright 1997, with the kind permission of Elsevier Science-NL, Sara Burgerhartstraat 25, 1055 KV Amsterdam, The Netherlands.)...

Free retinol is chemically unstable and does not occur to any significant extent in foods or tissues. Rather, it is present as a variety of esters, mainly retinyl palmitate. Retinyl acetate is generally used as an analytical standard and in pharmaceutical preparations. Dehydroretinol (vitamin A2) is found in freshwater fishes and amphibians it has about half the biological activity of retinol. 

Studies in vitamin A replete animals suggest that most of the retinol is transferred from hepatocytes to the perisinusoidal stellate cells of the liver. Here, it is again esterified by LRAT to form mainly retinyl palmitate (76% to 80%), with smaller amounts of stearate (9% to 12%), oleate (5% to 7%), and linoleate (3% to 4%). The stellate cells contain 90% to 95% of hepatic vitamin A, as cytoplasmic lipid droplets that consist of between 12% to 65% retinyl esters (Batres and Olson, 1987). Studies with [ C]retinyl palmitate show that much of the recently ingested retinol appears more or less immediately in the... 

There are some vitamins, which are adversely effected by exposure to UV-VIS radiation during administration if not photoprotected. Among the fat-soluble vitamins, vitamin A (retinol, retinyl palmitate) photodegradation is of clinical significance. 

Vitamin A supplementation programs have been used in Indonesia, the Phi lip-pi lies, and Africa, where they have resulted in moderate reductions in child mortality and dramatic decreases in the incidence of nightblindness and xerophthalmia. Public health workers have used the following schedule for preventing xerophthalmia and increasing the liver s resen es of vitamin A. Oral retinyl pa Imitate (110 mg), ret In y I acetate (6f> mg), or injected retinyl palmitate (. 5 mg) are administered on each of two successive days, and once a few weeks later if symptoms are not relieved, One approach that seems to be especially workable is to give high-dose capsules at the hme of a scheduled immunization. One clei- er... 

Simonne, A.H. and EitenmiUer, R.R. 1998. Retention of Vitamin E and Added Retinyl Palmitate in Selected Vegetable Oils during Deep-Fat Frying and in Fried Breaded Products. J. Agric. Food Chem. 46 5273-5277. 

The application of SCF to the extraction of vitamins has been widely reported. Thus, retinyl palmitate and tocopherol acetate have been extracted from a hydrophobic ointment with supercritical CO2 at 40°C and 196 bar for 4 min, the extract analysis being performed by SFC (137). The calibration graphs were linear from 0.5 to 2.5 pg and the recoveries were quantitative. On the other hand, water-soluble vitamins can be extracted mixing them with low substituted hydroxypropil cellulose. Portions were placed in a column to which a reversed micellar extractant was delivered (138). Extraction of vitamins A and E and their esters from tablet preparations prior to FIPLC was performed in the dynamic mode with CO2 at 40°C and 253 bar for 15 min (139). Calibration graphs were linear from 0.02 to 0.8 and from 0.005 to 0.2 mg/mL of vitamins E and A, respectively. The corresponding RSDs (six... 

Retinol (vitamin A alcohol), retinoic acid (vitamin A acid), retinyl acetate (vitamin A acetate), retinal (vitamin A aldehyde) and reinyl palmitate (vitamin A palmitate) See in... 

Vitamin A palmitate (retinyl palmitate) [79-81-2] M 524.9, m 28-29 , e (an-trans)lOOO (325 nm) in EtOH. The palmitate is separated from retinol by column chromatography on water-deactivated alumina with hexane containing a very small percentage of acetone. It is also chromatographed on TLC silica gel G, using pet ether/isopropyl ether/acetic acid/water (180 20 2 5) or pet ether/acetonitrile/acetic acid/water (190 10 1 15) to develop the chromatogram. It is then recrystallised from propylene at low temperature (below -47°). Beilstein 6 IV 4135.]... 

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