Fixed-Oil Excipient Monographs: Development of USP Fixed-Oil Reference Standards - Pharmaceutical Technology

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Fixed-Oil Excipient Monographs: Development of USP Fixed-Oil Reference Standards
This article summarizes the development and modernization of the United States Pharmacopeia-National Formulary (USP-NF) fixed-oil excipient monographs. This article contains bonus online-exclusive material.


Pharmaceutical Technology
Volume 37, Issue 4, pp. 102-108

Assay. Content of Triglycerides. In recent decades, advances in chromatography and spectrometric methods (including mass spectrometry) have provided significant advancements in the understanding of complex excipient mixtures.

Some fixed oils from different plant sources yield characteristic patterns with distinct triglycerides that predominate (9). In many cases, the triglyceride pattern is more representative of the fixed oil identity than the fatty acid composition. This pattern can be determined with the help of HPLC or GC. A test for Triglyceride Composition based on an HPLC procedure using a refractive index detector was included in Sesame Oil NF in USP 28−NF 23 (2005) (3). The test has an additional advantage because it can be performed on an intact sample, and it directly assesses the chemical composition of the oil and is recommended as an Assay or Composition test. If the test for Triglyceride Composition is introduced into fixed-oil monographs, it also can be used as a stand-alone identification test.

In recent years, instrument manufacturers have developed and introduced more universal and sensitive detectors such as the evaporative light scattering detector (ELSD) and the charged aerosol detector (CAD) to test nonchromophoric analytes. When analytical instruments’ reliability, availability, suitability, and affordability substantially improve, public standards using these analytical tools can be developed and published. During the modernization of the Lecithin NF monograph in recent years, EXC EC for the first time introduced a test for Content of Phospholipids based on HPLC/ELSD to determine and quantify each individual phospholipid in lecithin (22).

Castor oil is one of the few naturally occurring triglycerides with high purity because the fatty acid portion comprises nearly 90% of the unique hydroxylated fatty acid, ricinoleic acid C18H34O3, shown in Figure 4.

Ricinoleic acid is a major constituent of castor oil, and triricinolein is a major triglyceride in the product (25). Advances such as HPLC/ESLD and HPLC/CAD may provide opportunities to develop a test for Content of Triglycerides for castor oil and the other fixed oils.

High-performance size-exclusion chromatography (HPSEC) is a useful analytical tool to identify and quantify triglycerides, diglycerides, and monoglycerides, as exemplified in Glyceryl Monostearate NF, Glyceryl Distearate NF, and Glyceryl Tristearate NF, monographs in USP 36–NF 31 (2013) (26). In the Lipid Injectable Emulsion USP monograph, HPSEC is used to determinate soybean oil or other relevant oils used in the emulsion. Reports indicated that all triglycerides from soybean oil or other relevant oils are eluted as one peak under the test conditions, without separation. Although HPSEC cannot be used to differentiate fixed oils of different botanical origin, the amount of triglycerides in a fixed oil can be determined using the HPSEC procedure.


Table VIII: Iodine value and saponification value for fixed oils included in USP 31–NF 26 (Ref. 27).
Specific tests. Sterol Composition. The composition of fatty acids traditionally has been used as an indicator of purity, although the wide variation in the composition of edible oils from different geographical origins or different cultivars is a limiting factor in the interpretation of data with regard to adulteration. Sterols, which comprise a major portion of the unsaponifiable matter, are found in almost all fats and fixed oils, and they also are characteristic of the authentic fixed oil.

Sterols are highly specific for each oil source, and a sterol composition analysis can reveal the identity of the components in a mixture. The determination of the composition of sterols from unsaponifiable matter serves as a further test for purity. Such general tests for selected attributes—when used together—provide a robust and unique identification for the fixed oil.

USP staff and EM2 EC recommended that the tests of Fatty Acid Composition (from the saponifiable portion) and Sterol Composition (from unsaponifiable matter) be used orthogonally for certain fixed oils to determine their identity and quality. Because of characteristic sterol profiles and the high economic values of almond oil and olive oil, comprehensive Sterol Composition specifications have been implemented in both monographs. The Sterol Composition specifications in Soybean Oil USP and Corn Oil NF serve to exclude any other contaminating oils such as canola oil when these fixed oils are manufactured in the same facilities.


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