Simultaneous determination of metformin and glimepiride in human serum by ultra high performance liquid chromatography quadrupole time of flight mass spectrometry detection.

This work proposes a simple method for the simultaneous determination of two antidiabetic compounds, metformin and glimepiride, by ultra-high performance liquid chromatography using quadrupole time of flight mass spectrometry detection with electrospray ionization. The method was validated and shown to be linear, selective, accurate and precise. The chromatographic separation was performed using a BEH C18 column (50 mm x 2.1 mm, 1.7 µm particle size). The mobile phase was composed by 0.05% (v/v) aqueous formic acid solution and acetonitrile using a gradient elution program, at a flow rate of 0.3 mL/min. Linearity range for metformin was 1.7-100 µg·L-1, using propranolol as internal standard and 3.3-100 µg·L-1 for glimepiride using glibenclamide as internal standard. Limits of detection and lower limits of quantitation were 0.4 µg·L-1 and 1.7 µg·L-1 for metformin and 0.7 and 3.3 µg·L-1 for glimepiride, respectively. The method was used for the simultaneous determination of these compounds in human serum samples with lower limits of detection and quantitation than serum levels reported in previous works that allows its applicability in therapy drug monitoring.

LOW LEVELS OF SERUM CYANOCOBALAMIN IN A METFORMIN-TREATED PATIENT. CASE REPORT AND COMPARISON WITH LITERATURE DATA.

Metformin is a widely used oral antidiabetic biguanide compound. According to the literature, metformin may lower the serum cyanocobalamin levels. We present the case of a 71-old-male treated with metformin for 15 years. When presenting to a periodic checkup, low serum cyanocobalamin levels where found. Laboratory tests showed levels below normal range for hemoglobin (12.7 g/dL) and hematocrit (37.8%). After patient reevaluation, a change in antidiabetic treatment will be considered if metformin will be found the cause of low serum cyanocobalamin levels. Other cases reported in the literature support this hypothesis, justifying the study of the influence of metformin therapy on serum vitamin B12 levels in patients diagnosed with diabetes. The influence of patient age, metformin dosage, duration of treatment and time since diabetes diagnosis on serum levels of vitamin B12 also need to be determined.

FIXED DOSE COMBINATIONS WITH SELECTIVE BETA-BLOCKERS: QUANTITATIVE DETERMINATION IN BIOLOGICAL FLUIDS.

Hypertension is one of the most common causes of death, a complex and incompletely controlled disease for millions of patients. Metoprolol, bisoprolol, nebivolol and atenolol are selective beta-blockers frequently used in the management of arterial hypertension, alone or in fixed combination with other substances. This study presents the most used analytical methods for simultaneous determination in biological fluids of fixed combinations containing selective beta-blockers. Articles in Pub-Med, Science Direct and Wiley Journals databases published between years 2004-2014 were reviewed. Methods such as liquid chromatography--mass spectrometry--mass spectrometry (LC-MS/MS), high performance liquid chromatography (HPLC) or high performance liquid chromatography--mass spectrometry (HPLC-MS) were used for determination of fixed combination with beta-blockers in human plasma, rat plasma and human breast milk. LC-MS/MS method was used for simultaneous determination of fixed combinations of metoprolol with simvastatin, hydrochlorothiazide or ramipril, combinations of nebivolol and valsartan, or atenolol and amlodipine. Biological samples were processed by protein precipitation techniques or by liquid-liquid extraction. For the determination of fixed dose combinations of felodipine and metoprolol in rat plasma liquid chromatography--electrospray ionization--mass spectrometry (LC-ESI-MS/MS) was applied, using phenacetin as internal standard. HPLC-MS method was applied for the determination of bisoprolol and hydrochlorothiazide in human plasma. For the determination of atenolol and chlorthalidone from human breast milk and human plasma the HPLC method was used. The analytical methods were validated according to the specialized guidelines, and were applied to biological samples, thing that confirms the permanent concern of researchers in this field.

Statistical study on the incidence of allergic diseases treated with desloratadine and levocetirizine at "Atopia" Allergology Medical Center, Iasi, Romania.

UNLABELLED: Allergies and allergic manifestations are a major health problem in our country and around the world. Epidemiological data have reported an increased incidence of allergic diseases up to 10-30% over the past decades. AIM: To evaluate the incidence of the most common allergic diseases treated with desloratadine or levocetirizine, second-generation antihistamines. MATERIAL AND METHODS: For diagnosis and assessment of treatment with the two antihistamines the following tests were performed: allergy skin testing, immunoglobulin E blood levels, evaluation of target organ for allergic reaction (lung function tests, nasal and conjunctival examination, assessment of bronchial inflammation). RESULTS: We conducted a retrospective study that included 365 patients (64% women and 36% men) diagnosed with different types of allergy in the "Atopia" Allergology Medical Center at Iasi during the interval August 2012-August 2013. Patients were aged 2 to 90 years (mean age group 35.98 years; 39.55 years for women, and 29.74 years for men). CONCLUSIONS: The majority of patients were from urban areas (82%). The most common allergic diseases in the study group were: urticaria (21%), allergic rhinoconjunctivitis (14%), allergic bronchitis (14%) and allergic asthma (12%).

Metformin induced lactic acidosis--particularities and course.

Diabetes mellitus is a widespread disease with many serious chronic complications. An improvement in the oral antidiabetic medication in respect to its mechanism of action and toxicology was needed in order to have effective therapies with high compliance and minimum side effects. In this context, metformin is a widely used oral antidiabetic drug, which, through its mechanism of action, has no risk of hypoglycemia. However, a rare but serious side effect of biguanides is lactic acidosis. This paper presents a number of 13 cases of metformin-associated lactic acidosis, which outline the circumstances triggering the adverse event and the clinical therapeutic measures applied in the poisoned patients. The main situations that favor metformin-associated lactic acidosis are renal impairment and tissue hypoxia, and the intervention is adapted to the particular patient condition and symptoms, such as marked hypotension and cardiac arrest. Although there are commonalities in describing the consulted patients, the final prognosis is not dependent on the dose or metformin plasma levels, but rather on the associated pathologies and medication.