Determination of cocaine adulterants in human urine by dispersive liquid-liquid microextraction and high-performance liquid chromatography.

This study aimed to determine simultaneously five major street cocaine adulterants (caffeine, lidocaine, phenacetin, diltiazem, and hydroxyzine) in human urine by dispersive liquid-liquid microextraction (DLLME) and high-performance liquid chromatography. The chromatographic separation was obtained in gradient elution mode using methanol:water plus trifluoroacetic acid 0.15% (v/v) (pH = 1.9) at 1 mL min-1 as mobile phase, at 25 °C, detection at 235 nm, and analysis time of 20 min. The effect of major DLLME operating parameters on extraction efficiency was explored using the multifactorial experimental design approach. The optimum extraction condition was set as 4 mL human urine sample alkalized with 0.5 M sodium phosphate buffer (pH 12), NaCl (15%, m/v), 300 µL acetonitrile (dispersive solvent), and 800 µL chloroform (extraction solvent). Linear response (r2 ≥ 0.99) was obtained in the range of 180-1500 ng mL-1 with suitable selectivity, quantification limit (180 ng mL-1), mean recoveries (33.43-76.63%), and showing relative standard deviation and error (within and between-day assays) ≤15%. The analytes were stable after a freeze-thaw cycle and a short-term room temperature stability test. This method was successfully applied in real samples of cocaine users, suggesting that our study may contribute to the appropriate treatment of cocaine dependence or with the cases of cocaine acute intoxication.

Dispersive liquid-liquid microextraction based on solidification of floating organic drop and high-performance liquid chromatography to the analysis of cocaine's major adulterants in human urine.

A simple method has been proposed for the determination of cocaine's major adulterants (caffeine, levamisole, lidocaine, phenacetin, diltiazem, and hydroxyzine) in human urine by dispersive liquid-liquid microextraction based on solidification of floating organic drop (DLLME-SFO) in combination with high-performance liquid chromatography - photodiode array detector (HPLC-PDA). The reversed-phase chromatographic separation was obtained with a column C18 extended (250×4.6mm; 5µm; 80Å) in gradient elution mode using acetonitrile-trifluoroacetic acid 0.026% (v,v) (pH=2.5) at 1mLmin-1 as mobile phase, at 25°C, and detection at 235nm. The analysis time was 25min. This condition had the best resolution factors (>1.15), retention factors (>0.68), number of plates (>2094.9), and separation factors (>1.05) for all targets, indicating a good separation. The kind of extraction and dispersive solvent were investigated for unifactorial design. The buffer pH, the volume of extraction and disperser solvent, and the amount of salt were optimized for full factorial design. Under optimum conditions, human urine samples were alkalized with 0.5M sodium phosphate buffer (pH 10) and added to sodium chloride (20%m/v). Acetonitrile (150µL) and 1-dodecanol (30µL) were used as dispersive and extraction solvent, respectively. The method presented linear range of 312.5-3125ngmL-1 to caffeine and levamisole and 187.5-1875ngmL-1 to lidocaine, phenacetin, diltiazem, and hydroxyzine. The limit of quantification was 187.5ngmL-1 to lidocaine, phenacetin, diltiazem, and hydroxyzine and 312.5ngmL-1 for caffeine and levamisole. The recovery mean values were between 6.0 and 42.6%. The method showed good precision and accuracy, with within- and between-run relative standard deviation and relative error less than 15%. The samples were stable after freeze-thaw cycle and short-term room temperature stability tests. Besides, this method was satisfactorily applied in urine of cocaine users. It is expected that this method, which was the first to combine the use of DLLME-SFO and HPLC-PDA for the determination of cocaine's major adulterants in human urine, will contribute to the accuracy in the diagnosis of acute intoxication, the proper planning of therapeutic measures, as well as to the favorable prognostic of cocaine intoxicated patients.

Side effects of the therapy with peginterferon and ribavirin in chronic hepatitis C: a small audit.

This study sought to decribe, quantify, and classify any adverse reactions occurring in patients with chronic hepatitis C treated with peginterferon and ribavirin, as well as verify the occurrence of potential medication interactions. The most prevalent reactions were fatigue (84.8%), fever (83%), weight loss (80%), irritability (74%), and body pain (72%). Most of the reactions were classified as mild (95%), whereas 4.5% were classified as moderate and 0.4% as severe. Adverse reactions led to the rearrangement of therapy for 9 patients (20%), where there was a reduction in dose for 7 (15%), temporary interruption of treatment for 5 (11%), and permanent discontinuation for 3 patients (7%). A total of 11 potential medication interactions were identified in 9 patients (20%), with the most frequent between peginterferon-α2a and captopril (45%). Given the above, it is observed that the treatment of chronic hepatitis C is marked by several adverse reactions of varying severity, which can interfere with the patient's quality of life or in treatment compliance, and that can be aggravated by potential drug-drug interactions.