Rosa M. Jiménez

Quantitative determination of the calcium channel antagonists amlodipine, lercanidipine, nitrendipine, felodipine, and lacidipine in human plasma using liquid chromatography-tandem mass spectrometry.

A sensitive and specific liquid chromatography-tandem mass spectrometric method has been developed and validated for the quantification of the five 1,4-dihydropyridine calcium channel antagonists amlodipine, lercanidipine, nitrendipine, felodipine, and lacidipine in human plasma. Sample preparation involved solid-phase extraction on RP-C18 cartridges with good recovery for all the compounds. Sample analysis was performed on a Luna RP-C18 analytical column (15 mm × 2 mm ID, 3.0 μm) with a Sciex API 365 triple quadrupole mass spectrometer with turboionspray source and multiple reaction monitoring. The method is sensitive with a limit of detection below 1 ng/mL for each drug in plasma, with good linearity (r2 > 0.998), over the therapeutic concentration range (1 to 40 ng/mL). All the validation data, such as accuracy, precision, and interday repeatability, were within the required limits. The method can be used for pharmacokinetic studies and therapeutic drug monitoring of the compounds in humans.

Determination of the β-blocker atenolol in plasma by capillary zone electrophoresis

Abstract A capillary zone electrophoretic method was optimised for the determination of the β-blocker atenolol in plasma. Separation was performed in an uncoated silica capillary of 58.5 cm (effective length 50 cm)×75 μm I.D., and detection was at 194 nm. The effects of the buffer (concentration and pH), the injection time, the voltage applied and the plasma clean-up procedure were studied. The determination of atenolol was achieved in less than 3 min, using an electrolyte of 50 mM H3BO3–50 mM Na2B4O7 (50:50, v/v) pH 9, injected hydrodynamically for 4 s at 50 mbar and applying a voltage of +25 kV. This method was applied to the determination of atenolol in plasma of nine hypertensive patients (male and female, aged from 39 to 73 years). Atenolol concentrations found vary from 30 to 585 ng/ml.

Serum protein binding of propofol in patients with renal failure or hepatic cirrhosis

Background: Serum protein binding is a limiting factor in the access of drugs to the central nervous system. Disease‐induced modifications of the degree of binding may influence the effect of anesthetic drugs.

Electrochemical determination of the loop diuretics piretanide and furosemide in pharmaceutical formulations and urine

Abstract The oxidation of the loop diuretics 4-phenoxy-3-(1-pyrrolidinyl)-5-sulphamoylbenzoic acid (piretanide) and 4-chloro-2-furfurylamino-5-sulphamoylbenzoic acid (furosemide) was studied in methanol-water (10:90) in the pH range 0.3–13 (piretanide) and 0.5–13 (furosemide), with 0.04 mol/l Britton-Robinson buffers as supporting electrolytes and 0.5 mol/1 KCl as ionic medium at a glassy carbon electrode. Oxidation processes have shown to be irreversible and predominantly diffusion controlled over the whole pH range studied for both diuretics. Voltammetric methods have been developed for the determination of piretanide at pH 5.0 and furosemide at pH 4.5 using differential pulse and square wave voltammetry. The peak current showed a linear relationship with concentration up to 25 mg/l (6.9 × 10 −5 mol/l for piretanide and 5.5 × 10 −5 mol/1 for furosemide) with a reproducibility in terms of standard deviation ( n = 10) lower than 5.6%. A detection limit of 50 ng/l was obtained (1.38 × 10 −7 mol/l piretanide and 1.51 × 10 −7 mol/l furosemide) for both electroanalytical techniques. Methods proposed were applied to pharmaceuticals and spiked urine samples.

A high-performance liquid chromatographic method for screening angiotensin II receptor antagonists in human urine

SummaryA high-performance liquid chromatographic method with photometric detection has been developed for the determination of five angiotensin II receptor antagonists (ARA II): Losartan, Irbesartan, Valsartan, and Candesartan cilexetil and its metabolite Candesartan M1. Reversedphase chromatography was performed at room temperature on a μBondapak C18 column; compounds were separated by gradient elution with mixtures of acetonitrile and 0.1 M acetate buffer, pH 4, at different flow rates. Detection was at 254 nm. Urine samples were purified by solid-phase extraction on C8 cartridges, a procedure enabling recoveries > 85% for all the drugs except Candesartan cilexetil (71%). The analysis time was less than 50 min, including extraction (chromatographic analysis lasted 25 min). Intra- and inter-day coefficients of variation for all the compounds were below 8% and the method was highly accurate (relative error,RE, usually ca 3%). The accuracy, precision, and sensitivity (limit of quantitation 0.4 μg mL−1) of the method were sufficient for application to the screening of these ARA II in spiked urine samples.

Application of capillary zone electrophoresis to the screening of some angiotensin II receptor antagonists.

A capillary zone electrophoretic (CZE) method was optimized for the separation of five angiotensin II receptor antagonists (Losartan, Irbesartan, Valsartan, Telmisartan and Eprosartan) and two of their metabolites (EXP 3174 and Candesartan M1) by means of experimental design methodologies. The aim of this study was to define rapidly experimental conditions under which the analytes can be resolved for quantitation. The effects of the buffer (pH, concentration and composition), the organic modifier and voltage were studied. Critical factors were identified in a screening design (fractional factorial design) and sequentially an optimization design (central composite design) was used to choose optimal conditions for separation. The most favorable electrophoretic conditions were found by setting the resolution at a threshold value (Rs ≤ 1.5) and minimizing, if possible, analysis time. Successful results were obtained with a 50 mM potassium dihydrogen phosphate:boric acid (25:75 v/v) buffer at pH 5.5 in the presence of 5% methanol and application of a 25 kV voltage. Analysis time was 8 min in a conventional fused‐silica capillary (50 cm effective length) in a normal cationic mode (anode at the inlet and cathode at the outlet) after hydrostatical sample injection for 30 s.

Simultaneous Determination of the Diuretics Triamterene and Furosemide in Pharmaceutical Formulations and Urine by HPLC-EC

Abstract A high performance liquid chromatographic method with amperometric detection has been developed for the simultaneous determination of two diuretics: triamterene and furosemide, using a μ-Bondapak C18 column. The mobile phase consisted of a mixture water:acetonitrile, 30:70, 5mM in KH2PO4/K2HPO4, pH 5.5 pumped at a flow rate of 1 mL/min. The amperometric detector, equipped with a glassy carbon electrode, was operated at +1300 mV. The method was applied to the determination of both diuretics in the pharmaceutical formulation Salidur (triamterene 25 mg and furosemide-xanthinol 77.6 mg) and real urine samples obtained from a healthy volunteer after the ingestion of a single dose of Salidur. Using a simple liquid-liquid extraction procedure, good recovery and separation from interferences found in urine matrix is achieved and the simultaneous determination of both compounds is possible. Reproducibility is good with relative standard deviations lower than 1.5% intra-day and 5% inter-day, and the method...

Voltammetric study of the diuretic xipamide

Abstract The oxidative behaviour of 4-chloro-5-sulfamylsalicyloyl-2′,6′-dimethylamilide (xipamide) was studied in aqueous alcoholic media (9:91 MeOH+H 2 O, pH 1–7.5) and two different ionic media (KNO 3 and KCl) at carbon electrodes. The oxidation process has been shown to be irreversible and predominantly diffusion controlled over the entire pH range and in both media. A voltammetric method was developed at pH 2.5 (phosphate buffer) and 0.4 M KNO 3 for the quantitative determination of xipamide. The peak current showed a linear relationship with concentration in the range 4.65 × 10 −7 - 2.88 × 10 −5 M with detection limits of 6.76 × 10 −8 M (24 ppb) by differential pulse voltammetry and 3.94 × 10 −7 M (140 ppb) by linear scan voltammetry, and a reproducibility (in terms of relative standard deviation) of 5.8% and 6.3% for 10 determinations of concentrations of 1.41 × 10 −5 M and 7.05 × 10 −8 M respectively. The method for xipamide was applied to assays of pharmaceuticals (Demiax 20 mg) and spiked urine samples.

Micellar electrokinetic chromatography as a fast screening method for the determination of the doping agents furosemide and piretanide in urine

The possibility of using micellar electrokinetic chromatography for the screening of the loop diuretics piretanide and furosemide in urine was studied. A fast and simple method with good repeatability is described. The method was applied to urine samples collected from a healthy volunteer after oral administration of therapeutic doses of each compound. Positive identification in the urine matrix was possible through recording diode array spectra.

Voltammetric Study of the Synthetic Pyrethroid Insecticides Cypermethrin and Deltamethrin and Their Determination in Environmental Samples

The electrochemical reduction behavior of two synthetic α-cyano ester pyrethroid insecticides, cypermethrin and deltamethrin at a hanging mercury drop electrode (HMDE) is described by employing different voltammetric techniques and using a methanolic Britton-Robinson (B-R) buffer solution with tetrabutylammonium chloride (TBAC). The electrode process, nature and reversibility were examined by using cyclic voltammetry (CV) at different pH values. Furthermore, the kinetic parameter αcn was estimated for the different acidic zones and the number of electrons involved in the reduction mechanism was found to be two at pH values 2–12. A possible reduction mechanism is proposed, and a quantitative voltammetric method was developed for the determination of cypermethrin and deltamethrin in agricultural formulations, water and soil samples.