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Previous hepatitis associated with INH.

These methods have high specificity and are designed to analyse hydrazine metabolites in addition to INH and acetylINH, for use in metabolic and pharmacokinetic research (see for example, Lauterberg et al., 1981). 8.2.2.5 Other dedicated method(s) 8.2.3 Interpretation of toxicological analyses

INH may induce acute hepatitis, peripheral neuropathy, haemolytic anaemia.
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INH should not be used in patients with acute liver disease.

Measurement of INH serum levels are not useful for the clinical management of INH overdose.
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Characteristic fragmentation is achieved on mass spectrometry, and the most abundant ions are: INH m/z 78, 106, 51 and 137; INH-TFAA m/z 215, 78, 106, 146; INH-diTMS m/z 73, 75, 266, 147 and 117.

Quantitation is performed by addition of a suitable internal standard, and comparison of the response of the material to the analysis of known amounts of INH prepared similarly.

INH penetrates well into caseous lesions.

INH produces pharmacologic changes in pyridoxine metabolism (Biehl & Vitter, 1954):
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Chromatographic measurement of INH and metabolites in biological materials is possible after extraction into a polar organic solvent or precipitation of proteins.

Measurement of INH is not affected by administration of pyridoxine antidote, and although INH pyridoxine hydrazone can be seen in urine, it is also produced post-renally.

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There is a cross resistance between INH, rifampicin and ethambutol.

As a guide, the following table shows typical concentrations of INH in serum. 8.3.1 Biochemical analysis 8.3.1.1 Blood, plasma or serum - 8.3.1.2 Urine 8.3.1.3 Other fluids 8.3.2 Arterial blood gas analyses 8.3.3 Haematological Analyses

Whole blood with anticoagulant and glycolytic inhibitor (e.g.

The rapid distribution kinetics of INH, and relatively short elimination half-life (1 to 2 hours in fast, and 3 to 5 hours in slow acetylators) means that serum concentrations fall sharply, and can be only a fraction (20%) of the peak within 5 or 6 hours.

Some methods additionally quantify acetylINH.

Some methods are only suited to the analysis of intact INH (LoDico et al., 1992; Stewart et al., 1995), or are limited by sample volume to urine (Timbrell et al., 1977).

Phenytoin metabolism is inhibited by INH.

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INH is classified as category C by Briggs et al.

Urine must be treated with dilute hydrochloric acid (15 minutes at room temperature) to ensure conversion of acid labile hydrazones back to INH, to reflect urinary excretion reliably since these compounds are thought to be produced in the bladder.

Intravenous: 1 g pyridoxine for each 1 g INH ingested.

Urine is generally incubated at room temperature for 15 minutes with 0.1 M HCl to hydrolyze acid-labile hydrazones back to INH prior to analysis in order to reflect urinary excretion reliably since these compounds are thought to be produced in the bladder (Svensson et al., 1985; Khono et al., 1991).

[Synthesis of pyridylmethylamides of isonicotinic acid].

[41] Seyyedi, N., Shirini, F., and Langarudi, M.S.N., 2016, DABCO-based ionic liquids: green and recyclable catalysts for the synthesis of barbituric and thiobarbituric acid derivatives in aqueous media, RSC Adv., 6 (50), 44630–44640.

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