PMID- 11820293 OWN - NLM STAT- MEDLINE DCOM- 20020502 LR - 20190922 IS - 1570-0232 (Print) IS - 1570-0232 (Linking) VI - 766 IP - 1 DP - 2002 Jan 5 TI - Therapeutic isoniazid monitoring using a simple high-performance liquid chromatographic method with ultraviolet detection. PG - 181-7 AB - Simultaneous measurement of isoniazid and its main acetylated metabolite acetylisoniazid in human plasma is realized by high-performance liquid chromatography. The technique used is evaluated by a factorial design of validation that proved to be convenient for routine drug monitoring. Plasma samples are deproteinized by trichloroacetic acid and then the analytes are separated on a microBondapak C18 column (Waters). Nicotinamide is used as an internal standard. The mobile phase is 0.05 M ammonium acetate buffer (pH 6)-acetonitrile (99:1, v/v). The detection is by ultraviolet absorbance at 275 nm. The validation, using the factorial design allows one to: (a) test the systematic factors of bias (linearity and matrix effect); (b) estimate the relative standard deviations (RSDs) related to extraction, measure and sessions assay. The linearity is confirmed to be within a range of 0.5 to 8 microg/ml of isoniazid and 1 to 16 microg/ml of acetylisoniazid. This method shows a good repeatability for both extraction and measurement (RSD INH=3.54% and 3.32%; RSD Ac.INH=0.00% and 5.97%), as well as a good intermediate precision (RSD INH=7.96%; RSD Ac.INH=15.86%). The method is also selective in cases of polytherapy as many drugs are associated (rifampicin, ethambutol, pyrazinamide, streptomycin). The matrix effect (plasma vs. water) is negligible for INH (3%), but statistically significant for Ac.INH (11%). The application of this validation design gave us the possibility to set up an easy and suitable method for INH therapeutic monitoring. FAU - Moussa, L Ait AU - Moussa LA AD - Laboratoire de Toxicologie d'Urgence et de Suivi Therapeutique, Centre Anti-Poisons du Maroc, Institut National d'Hygiene, Rabat. FAU - Khassouani, C E AU - Khassouani CE FAU - Soulaymani, R AU - Soulaymani R FAU - Jana, M AU - Jana M FAU - Cassanas, G AU - Cassanas G FAU - Alric, R AU - Alric R FAU - Hue, B AU - Hue B LA - eng PT - Journal Article PL - Netherlands TA - J Chromatogr B Analyt Technol Biomed Life Sci JT - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JID - 101139554 RN - 0 (Antitubercular Agents) RN - V83O1VOZ8L (Isoniazid) SB - IM MH - Antitubercular Agents/*blood MH - Chromatography, High Pressure Liquid/*methods MH - Drug Monitoring/*methods MH - Humans MH - Isoniazid/*blood MH - Reproducibility of Results MH - Spectrophotometry, Ultraviolet/*methods EDAT- 2002/02/01 10:00 MHDA- 2002/05/03 10:01 CRDT- 2002/02/01 10:00 PHST- 2002/02/01 10:00 [pubmed] PHST- 2002/05/03 10:01 [medline] PHST- 2002/02/01 10:00 [entrez] AID - S0378-4347(01)00434-0 [pii] AID - 10.1016/s0378-4347(01)00434-0 [doi] PST - ppublish SO - J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Jan 5;766(1):181-7. doi: 10.1016/s0378-4347(01)00434-0.