Simultaneous quantification of isoniazid,rifampicin, ethambutol and pyrazinamide by liquid chromatography/tandem mass spectrometry

A remediable cause of poor treatment response in drug‐susceptible tuberculosis (TB) patients may be low plasma levels of one or more of the first‐line anti‐TB drugs. The aim of this work was to develop an accurate and precise LC‐MS/MS method for simultaneous quantification of all four first‐line anti‐TB drugs in plasma suitable for therapeutic drug monitoring (TDM). To adjust for degradation and losses during sample preparation, isotopically labeled compounds were used as internal standards. Plasma samples spiked with internal standards were extracted using protein precipitation with methanol and acetonitrile. Simultaneous separation of all four drugs was accomplished with a Chromolith Reversed‐Phase column and mobile phases consisting of water, methanol, ammonium acetate and formic acid with subsequent mass spectrometric quantification. The linear range of the calibration curve for isoniazid was 0.5–10 mg/L, for rifampicin 0.75–30 mg/L, for ethambutol 0.25–10 mg/L and for pyrazinamide 4–80 mg/L. The lower limit of quantification was 0.5 mg/L, 0.75 mg/L, 0.25 mg/L and 4.0 mg/L, respectively. Precision estimated by the coefficient of variation was <15% for all four drugs. The LC‐MS/MS method can readily be used for simultaneous quantification of first‐line anti‐TB drugs in plasma and is well suited for TDM.     

Dental age estimation of Omani children using Demirjian's method

Dental age plays a significant role in forensic dentistry, orthodontics and paediatric dentistry, as well as in general diagnosis and treatment planning. Different methods have been developed to determine dental age. One of the most commonly used methods is Demirjian’s method, which was developed in 1973 from research on a large number of French-Canadian children. It is based on the degree of tooth mineralisation by examining the radiological appearance of the lower mandibular left quadrant. The purpose of this study was to assess the dental age of Omani children using Demirjian's method and evaluate the applicability of the method in dental age estimation for Omani children. The sample consisted of 485 digital panoramic radiographs of children (264 males, 221 females) aged between 4.6?years and 16.5?years, and obtained from the records of the Military Dental Centre in Oman. The data were analysed using SPSS. Paired t-tests, intraclass correlation coefficients (ICC) and difference-against-mean plots were used to compare the dental age calculated by Demirjian's method with chronological age. A single examiner scored the radiographs, and intra-observer reliability was evaluated using Cronbach's alpha on data from rescoring one out of every 20 radiographs. For boys, the mean difference between chronological age and dental age for all age groups was 0.10 (95% CI ?0.03 to 0.24). For girls, the mean difference between chronological age and dental age for all age groups was 0.05 (95% CI ?0.11 to 0.22). Difference-against-mean plots showed no evidence of differential bias by age. For boys, the ICC was 0.896 (95% CI 0.869–0.917); for girls, it was 0.886 (95% CI 0.854–0.911). Difference-against-mean plots for boys (Fig. 1) and girls (Fig. 2) showed some evidence of differential bias by age. In conclusion, the extent of the observed differences was sufficient for doubt to be cast upon the utility of Demirjian’s method for Oman, particularly when it is considered that the method’s most likely application would be in age determination for minors in the workforce.