Barbiturates ionisation

Barbituric acid (83) may be regarded as 2,4,6-trihydroxypyrimidine, but in the crystalline state it exists as the triketo-form (95). In aqueous solution the compound is remarkedly acidic as the result of ionisation of the mono-enolic form (96) with the formation of a resonance stabilised anion (97). 

The 11.7 eV lamp gives an almost imiveislower energy give some degree of selectivity. Compounds with an ionisation potential below that of the lamp will not be detected. Substances such as formaldehyde, hydrogen sulphide, nitrous oxide, tetraethyl lead, phosphine, and ammonia can be detected at bett sensitivities and wider dynamic range than with oth detectors. The barbiturates can be detected at low levels than with the flame ionisation detector. 

Fig. 2. Effect of pH on the ultraviolet spectrum of phenobarb-itone. A, non-ionised barbiturate in 0.1 M hydrochloric acid B, mono-anion in 0.05M borax buffer (pH 9.2) C, di-anion in 0.5M sodium hydroxide (pH 13).

Fluorescence is generally more sensitive to environmental factors than absorbance measurements. Signal intensity may be affected by pH, temperature, quenching, interfering substances, solvent, or interference from Rayleigh and Raman scattering. Many fluorescent species contain ionisable groups whose fluorescent properties are sensitive to pH. In some cases only one of the ionised species may be fluorescent. An example is the barbiturates which only fluoresce at elevated pH in the di-anionic form. The relationship of fluorescence intensity with pH should always be examined as part of the development of the method. 

Barbiturates are cyclic imides used as hypnotics and (in the case of pheno-barbital) as anticonvulsants. They are all derivatives of barbituric acid (which is not pharmacologically active) and differ only in their substituents on the 5-position of the ring. Barbiturates contain nitrogen atoms, but the lone pair on the nitrogen is not available for reaction with protons, so barbiturates are not basic. Instead, they behave as weak acids in solution (diprotic actually, though the second ionisation is very weak) the negative... 

Urinary alkalinisation increases the urine elimination of certain poisons by shifting the urine pH above 7.5 [1,21,79]. It is achieved by intravenous injection of a sodium bicarbonate solution. Raised pH of urine facilitates elimination of acidic drugs such as salicylates and barbiturates as they become ionised. The rate of reabsorption of an ionised drug into the blood is significantly lower than that of a non-ionised drug [1, 79]. In all cases however AC administration is more efficient than urinary alkalinisation [1,80]. It should be also kept in mind that WBI and urinary alkalinisation are relatively slow procedures which may cause delay with AC administration. 

The sodium salts of the barbiturates (monoanions) are usually quite soluble in water, and this is normally the preferred form of the drugs for therapeutic use. The stability and hydrolysis products of barbiturate salts have been reviewed in detail elsewhere [99], and will not be discussed here. The anions of the barbiturates are not soluble in lipids, and the non-ionised form of the hypnotic barbiturates is considered to be the active form of the drugs. Hence, an accurate knowledge of their dissociation constants and the pH values of solutions under the conditions of a given experiment are of considerable importance. The relationship of physical properties to physiological activity is discussed in the following section on the hypnotic barbiturates. 

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