Zs. Budvári-Bárány

Optimized and validated HPLC methods for compendial quality assessment. III. Testing of optical purity applying α1-acid-glycoprotein stationary phase

Abstract Since distomer impurity in the compendia enantiomer may indicate the lack of careful purification or an ability of racemization, the control of enantiomeric purity has growing significance. Although α1 - acid - glycoprotein (AGP) stationary phase was applied for the separation of a number of drug enantiomers, it was hardly used for testing of enantiomer purity. In this work the suitability of AGP column for compendial control of enantiomeric purity is illustrated by methods optimized through the selection of optimal quality (phosphate, acetate), pH (4.0; 5.5; 6.0; 7.0) and concentration (0.01, 0.03, 0.06 M) of the buffer-eluent and the best organic modifier (isopropanol, acetonitrile, dioxane). The chromatographic behavior of four basic, three acidic, and one neutral compound is interpreted. In the case of propranolol and ibuprofen, 5% impurity may be detected while, in the case of norgestrel, 2.5% of the impurity may be detected. Recommendations for compendial testing are presented.

Ion-Pair Chromatography of Nitrogen-Bridged Compounds on Silica Gel

Abstract New adsorption operations of high-performance ionpair chromatography have been investigated, using certain types of pharmacologically active nitrogen-bridged compounds. Various chromatographic data are reported. The effect of the counter ion concentration has been studied. Numerous examples of separations are presented.

OPTIMIZED AND VALIDATED HPLC METHODS FOR COMPENDIAL QUALITY ASSESSMENT. IV. NON-CHIRAL AND CHIRAL PURITY TESTS FOR SOLANACEOUS (TROPANE) ALKALOIDS

The main alkaloids of certain plants of the Solanacea family, such as atropine and scopolamine, together with the synthetic homatropine and methylhomatropine, are routinely used medicinal agents and have their monographs in the modern pharmacopeias. In these monographs, non selective chemical reactions and/or TLC serve for the detection of “foreign alkaloids, related substances, etc.” impurities. In the present paper selective HPLC methods for the compendial purity control of these alkaloids are published. The methods allow the detection of 0.05 μg (= 0.1 %) and the quantitation of 0.05 - 5.0 μg of tropic acid or mandelic acid as hydrolytic degradation product impurities (chromatographic system : C18/methanol - phosphate buffer pH 5 - 5.5). The limit of detection is 0.025 μg. Also, HPLC for the separation of tropane alkaloid enantiomers (chromatographic system : Chiralcel OD/n-hexane - isopropanol - methanol - triethylamine) is presented. Procedure for the enantiomeric purity control of S - (−) - hyoscyam...

Investigation of Structure-Property Relationships for Imidazoquinolone Derivatives. I. Relation Between Partition Coefficient and Chromatographic Retention

Abstract New imidazoguinazolone derivatives as potential pharmacons, prepared in our laboratory, have been studied by HPLC and TLC methods. As a part of a structure-properties research study (SPR) this paper deals with the relationship between the chemical structure of the compounds and their chromatographic retention. A good correlation has been found between log k′ or RM and the concentration of the organic modifier in mobile phase, as well as log k′ or RM and log P. On the basis of the measured retention data, log P prediction was made for compounds with very poor water-solubility.

Reversed-Phase Ion-Pair Chromatography of Nitrogen-Bridged Compounds

Abstract The retention times and resolution factors of certain types of pharmacologically active nitrogens-bridged compounds have been investigated using reversed-phase operations of high-performance ion-pair chromatog-raphy. Factors studied included the effect of the pH of the mobile phase, the influence of the nature and concentrations of the mobile phase components, and the effects of various counter ions. Numerous examples of separations are presented.

Optimized and validated HPLC Methods for Compendial Quality Assessment I. Methylxanthine Derivatives

Abstract The HPLC method suggested here is suitable for the detection and quantitative determination of 0.1–1 % caffeine, theobromine and theophylline impurities in each of these methylxanthine derivatives. The system optimization includes organic modifier content, ionic strength, eluent flow rate and concludes to the use of a simple C18/methanol-water 1:4 (I = 0.1) chromatographic system. The limit of impurity detection was found to be 15 ng (theobromine, theophylline) and 30 ng (caffeine). The range of quantitation extends from 31.25 to 250 ng. The accuracy (percentage of recovery) and precision (repeatability) of the method are tabulated. The method, considering validation requirements of USP XXIII, demonstrates the suitability of HPLC for selective compendial purity tests.

Some New Data Concerning The Chromatographic Purity Test for Nifedipine

Abstract The analysis of different Nifedipine commercial samples indicated the presence of impurities other than the nitroso- and nitrophenylpyridine analogues of Nifedipine generally are included in the pharmacopoeia-monographs. Besides the two latter photodegradation products isonifedipine and a tetrahydropyrimidine derivative as by products of nifedipine-synthesis were identified. HPLC procedure is suitable for the separation Nifedipine and all of the four contaminants is published.

Adsorption HPLC investigation of nitrogen-bridged compounds

Abstract Twenty two of tricyclic nitrogen bridged derivatives were examined by HPLC method in Zorbax SIL/chloroform–methanol system. Relationship between chemical structure (ring size, ring sequence, position of methyl substitution) and chromatographic behaviour is discussed.

Optimized and validated HPLC methods for compendial quality assessment. II. Opium alkaloids

Abstract The main opium alkaloids, such as morphine, codeine and papaverine have their own monographs in the modern pharmacopoeias. This paper includes reversed phase high performance liquid chromatographic procedures for the purity control of the mentioned opiates. The optimized and validated methods make possible the separation of morphine, codeine, thebaine, noscapine, papaverine and the detection of the four opiate impurities in morphine, codeine and papaverine. The limit of detection ranges from 0.01 up to 0.1%. Also, morphine content in codeine chloride can be quantitated with good accuracy.

Hplc of antiphlogistic acids on silica dynamically modified with cetylpyridinium chloride

Abstract The cetylpyridinium chloride (CPC) which contains an aromatic ring and a hydrophobic cetyl group differs in its structure from the generally used cationic counter ions. Thirteen of antiphlogistic acids and their derivatives were investigated. Silica as a stationary phase and an eluent containing CPC were used. The conclusion can be drawn that CPC functions as an ion pairing agent and its use in the aqueous eluent results in the formation of a „dynamically modified“ silica surface. The adsorption isotherm for CPC on the bare si] ica also was determined. Comparative data are shown on the retention of several antiphlogistic acids with CPC and cetrimide containing aqueous eluents.