Anaesthetics, local Sulphonamides

This type of titration is quite simple to carry out and is very useful for the analysis of sulphonamide antibiotics and aminobenzoic acid-derived local anaesthetics. Titration is carried out with acidified sodium nitrite causing the primary aromatic amine function to be converted to a diazonium salt shown in Figure 3.15 for sulphacetamide. 

Methaemoglobinaemia may be induced by oxidising drugs sulphonamides, nitrites, nitrates (may also occur in drinking water), primaquine, -caine local anaesthetics, dapsone, nitrofurantoin, nitroprusside, vitamin K analogues, chlorates, aniline and nitrobenzene. In the rare instance of there being urgency, methylene blue 1 mg/kg slowly i.v. benefits within 30 min. (Ascorbic acid competes directly with the chemical cause but is inadequate in severe cases, which are the only ones that need treatment.)... 

Moniero et al.[24] developed an indirect AAS method for the determination of local anaesthetics (lidocaine. tetracaine and procaine hydrochlorides) in pharmaceutical preparations using FI on-line precipitation-dissolution. A cobalt solution is injected into a carrier stream containing the sample, and the precipitate formed is retained on an online stainless steel filter. The determinations were made by measuring the residual cobalt concentration in a similar way as for the indirect determination of sulphonamides (cf. Sec. 9.4.2). A sampling frequency of 100 h was achieved with a precision of 0.6% r.s.d.. 

The method of Bratton and Marshall was developed for the estimation of sulphonamides in body fluids for mixtures in which the concentration of sulphonamides is sufficiently large (this also generally applies to urine) the determination is done as for the filtrate in the method described below. The absence of substances such as local anaesthetics, which would give the same colour reaction as the sulphonamides, must be ascertained. To determine the total drug if conjugated sulphonamides are present a portion of the prepared test solution must be hydrolysed by heating on a water-bath for one hour in 0-2N hydrochloric acid and subsequent adjustment to volume. The following method is that applied to blood ... 

The sulphonamides have a bacteriostatic rather than a bactericidal action. Many local anaesthetics used in the eye are esters of para-aminobenzoic acid and such drugs will interfere with the action of sulphonamides. To obtain the maximum effect from instillation of sulphonamide eye-drops these drugs should therefore not be used until the end of the waiting period allowed for the effect of the local anaesthesia to wear off before the patient departs. 

Aromatic amines are very weak due to the electron withdrawing effect of the benzene ring and aniline (Fig. 3.10) has a pKa value of 4.6. The presence of a second aromatic ring as in diphenylamine (Fig. 3.10) reduces the pKa value of the amine to 0.8. The presence of other electron withdrawing substituents in an aromatic ring either ortho or para to an aromatic amine group also reduces its pKa value. The pKa values of the aromatic amine groups found in sulphonamides such as sulfacetamide and some local anaesthetics such as procaine are ca. 2. 

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