Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive Aspergillosis.

PURPOSE: Invasive aspergillosis is a prevalent fungal disease, especially in Asian countries with a high mortality rate. Voriconazole (VRZ) is the first choice for invasive aspergillosis treatment. Plasma concentration of this drug is unpredictable and varies among individuals. This variability is influenced by many factors leading to clinical implication. Therapeutic drug monitoring (TDM) may have a crucial role in the patients' treatment process. The HPLC method provides sufficient specificity and sensitivity for plasma VRZ concentration determination for TDM purposes of this drug. METHODS: Patients who initiated oral or intravenous VRZ for invasive aspergillosis were enrolled in this study. Demographic characteristics and clinical data, outcome, and adverse effects were documented. For each patient, the plasma sample was collected under steady-state condition and analyzed using a validated HPLC method. RESULTS: A total of 22 measurements were performed. Fifty percent of patients were out of the therapeutic range. From them, 27.27% and 22.73% were in subtherapeutic and supratherapeutic ranges (<1 µg/mL and >5.5 µg/mL), respectively. There was a significant correlation between VRZ plasma concentration and treatment outcomes (P=0.022). Treatment failure was five times higher than treatment success in those in the subtherapeutic range. Adverse effects were observed more frequently in patients with supratherapeutic concentrations compared to those with non-supratherapeutic levels. Furthermore, the mortality rate in patients experiencing treatment failure was 2.17 times higher than those with treatment success. CONCLUSIONS: TDM of VRZ plays an important role in better evaluation of efficacy and toxicity during treatment. Therefore, determination of the drug level may be of clinical significance.

Simultaneous Determination of Isoniazid, Pyrazinamide and Rifampin in Human Plasma by High-performance Liquid Chromatography and UV Detection.

Therapeutic Drug Monitoring (TDM) of first-line anti-tuberculosis (TB) drugs is a decisive tool, allowing the clinician to successfully treat TB patients. The objective of the study was to develop and optimize a simple, sensitive, and reliable high-performance liquid chromatography (HPLC) method for the simultaneous determination of isoniazid (INH), pyrazinamide (PZA), and rifampin (RIF) levels in human plasma. Nicotinamide was used as the internal standard and the samples were prepared after protein precipitation using acetonitrile and zinc sulfate. The separation was achieved using a C18 reversed-phase applying gradient elution. The mobile phase was a combination of water-methanol solution with a ratio of 95:05 (v/v) at the initial phase. All calibration curves had good linearity (r2 > 0.99) and the inter- and intra-day RSDs were lower than 15%. The limit of detection with a signal-to-noise ratio (S/N) of 3:1 was 0.16, 0.5, and 0.33 µg mL-1 for INH, PZA, and RIF, respectively. The method presented here was selective, sensitive, and reproducible, and could be used for| therapeutic drug monitoring in the patients who were under treatment with these drugs.

Development and Validation of a Reversed-phase HPLC Method for Assay of the Decapeptide Cetrorelix Acetate in Bulk and Pharmaceutical Dosage Forms.

A gradient reversed-phase high performance liquid chromatography (HPLC) method was developed for the assay of cetrorelix acetate, a synthetic decapeptide with gonadotropin-releasing hormone (GnRH) antagonistic activity used in infertility treatment. The HPLC method, which is used to determine cetrorelix in bulk and pharmaceutical dosage forms, was validated per ICH guidelines. The chromatographic separation was achieved on a C18 reversed-phase column using acetonitrile, water and trifluoroacetic acid (TFA) as mobile phase and wavelength was set at 275 nm. The calibration curve was linear (r2 = 0.999) over cetrorelix concentrations ranging from 62.50 to 12.50 µg/mL (n = 6). The limits of detection (LOD) and quantification (LOQ) were calculated from the peak-to-noise ratio as 15.6 and 62.5 µg/mL, respectively. The method had an accuracy of > 97% and intra- and inter-day RSD of < 0.3% and < 1.6%, respectively and was validated with excellent specificity, sensitivity, and stability. The validated method was successfully applied for determination of cetrorelix in bulk and pharmaceutical dosage forms.

Increasing the number of adverse drug reactions reporting: the role of clinical pharmacy residents.

Detection of adverse drug reactions (ADRs) in hospitals provides an important measure of the burden of drug related morbidity on the healthcare system. Spontaneous reporting of ADRs is scare and several obstacles to such reporting have been identified formerly. This study aimed to determine the role of clinical pharmacy residents in ADR reporting within a hospital setting. Clinical pharmacy residents were trained to report all suspected ADRs through ADR-reporting yellow cards. The incidence, pattern, seriousness, and preventability of the reported ADRs were analyzed. During the period of 12 months, for 8559 patients, 202 ADR reports were received. The most frequently reported reactions were due to anti-infective agents (38.38%). Rifampin accounted for the highest number of the reported ADRs among anti-infective agents. The gastro-intestinal system was the most frequently affected system (21.56%) of all reactions. Fifty four of the ADRs were reported as serious reactions. Eighteen of the ADRs were classified as preventable. Clinical pharmacy residents' involvement in the ADR reporting program could improve the ADR reporting system.