Supercritical fluid extraction of 13-cis retinoic acid and its photoisomers from selected pharmaceutical dosage forms.
13-Cis retinoic acid (Accutane) was extracted from a cream, gel, capsule and beadlet dosage from using supercritical carbon dioxide modified with 5% methanol as the mobile phase. The pump pressure and the extraction chamber and restrictor temperature were experimentally optimized at 325 atm and 45 degrees C, respectively. A 2.5-min static and 5-min dynamic extraction time were used. The supercritical fluid extraction (SFE) eluent was trapped in methanol, injected into the high-performance liquid chromatographic (HPLC) system, and quantitated by ultraviolet detection at 360 nm. Application of the SFE method to spiked placebo dosage forms gave 13-cis retinoic acid recoveries of 98.8, 98.9, 98.8 and 100% for the cream, gel, capsule and beadlet, respectively, with R.S.D.s in the range 0.6-0.9% (n = 4). Inter-day percent error and precision of the extraction were 1.1-2.0 and 0.2-2.4% (n = 3), respectively, and intra-day percent error and precision were 1.0-3.0 and 0.3-2.1% (n = 8), respectively. Percent error and precision data for spiked celite samples in the 0.05-1.0 microgram ml-1 range were 0.59-4.75 and 1.8-2.1% (n = 3), respectively. The extraction method was applied to commercial 13-cis retinoic acid dosage forms and the results compared to unextracted samples. Linear regression analysis of concentration versus peak height gave a correlation coefficient of 0.9991 with a slope of 7.468 and a y-intercept of 0.1923. The percent error and precision data were 1.3-5.3 and 0.2-1.5% (n = 4), respectively. The photoisomers of 13-cis retinoic acid were also extracted with the method and recoveries of 90.4-92.4% with R.S.D.s of 1.5-3.4% were obtained (n = 4).
Simmons
B R
BR
Department of Medicinal Chemistry, College of Pharmacy, University of Georgia, Athens 30602-2352, USA.
Chukwumerije
O
O
Stewart
J T
JT
D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D007536:Isomerism; D015474:Isotretinoin / Q000032:analysis* / Q000737:chemistry; D010777:Photochemistry; D012044:Regression Analysis; D012996:Solutions; D013607:Tablets; D014212:Tretinoin
D002214:Capsules; D007202:Indicators and Reagents; D012996:Solutions; D013607:Tablets; D014212:Tretinoin; D015474:Isotretinoin