Physicochemical stability of nefopam and nefopam/droperidol solutions in polypropylene syringes for intensive care units.

Introduction: Nefopam has been reported to be effective in postoperative pain control with an opioid-sparing effect, but the use of nefopam can lead to nausea and vomiting. To prevent these side effects, droperidol can be mixed with nefopam. In intensive care units, high concentrations of nefopam and droperidol in syringes can be used with a continuous flow. Objectives: The first objective of this work was to study the physicochemical stability of a nefopam solution 2.5 mg/mL diluted in NaCl 0.9% in polypropylene syringes immediately after preparation and after 6, 24 and 48 hours at room temperature. The second objective was to study the physicochemical stability of mixtures of nefopam 2.5 mg/mL and droperidol 52 µg/mL diluted in NaCl 0.9% in polypropylene syringes at room temperature over 48 hours. Materials and methods: Three syringes for each condition were prepared. For each time of analysis, three samples for each syringe were prepared and analysed by high performance liquid chromatography coupled to photodiode array detection. The method was validated according to the International Conference on Harmonisation Q2(R1). Physical stability was evaluated by visual and subvisual inspection (turbidimetry by UV spectrophotometry). pH values were measured at each time of analysis. Results: Solutions of nefopam at 2.5 mg/mL and the mixture of nefopam 2.5 mg/mL with droperidol 52 µg/mL, diluted in NaCl 0.9%, without protection from light, retained more than 90% of the initial concentration after 48 hours storage at 20-25°C. No modification in visual or subvisual evaluation and pH values were observed. Conclusion: Nefopam solutions at 2.5 mg/mL and the mixture of nefopam 2.5 mg/mL with droperidol 52 µg/mL diluted in NaCl 0.9% were stable over a period of 48 hours at room temperature. These stability data provide additional knowledge to assist intensive care services in daily practice.

Stability-indicating HPLC assays for the determination of piritramide and droperidol in PCA solution.

WHAT IS KNOWN AND OBJECTIVE: A mixture of morphine and droperidol is a well-established antiemetic for reducing the risk of postoperative nausea and vomiting. A mixture of piritramide and droperidol has not yet been evaluated in this context. Our objectives were to develop a high-performance liquid chromatographic assay for piritramide and droperidol in 0·9% saline, and to establish their stability under defined storage conditions. METHODS: The separation and assay of both drugs were attempted by high performance liquid chromatography (HPLC) using a RP-select B column and a mobile phase of 57:43% v/v methanol-monosodium phosphate solution 0·05 M at a flow rate of 1·2 mL/min. UV detection at 205 and 246 nm for piritramide and droperidol were used, respectively. RESULTS AND DISCUSSION: The HPLC method was successful. Linearity was shown for piritramide from 0·075 to 0·013 mg/mL and for droperidol from 0·8 to 0·2 mg/mL. The intra- and inter-day relative standard deviation (RSD, %) was 0·27% and 0·54% for piritramide and droperidol, respectively. The two drugs were stable for at least 72 h when stored under ambient light at room temperature. WHAT IS NEW AND CONCLUSION: Seventy-five milligrams piritramide and 2·5 mg droperidol diluted to 50 ml with 0·9% saline should be suitable for clinical use. At this dilution, a Dipidolor(®) and Xomolix(®), mixture, was stable when stored under ambient light exposure at room temperature for at least 72 h.

Simultaneous RP-HPLC-DAD quantification of bromocriptine, haloperidol and its diazepane structural analog in rat plasma with droperidol as internal standard for application to drug-interaction pharmacokinetics.

A simple and rapid RP-HPLC-DAD method was developed and validated for simultaneous determination of the dopamine antagonists haloperidol, its diazepane analog, and the dopamine agonist bromocriptine in rat plasma, to perform pharmacokinetic drug-interaction studies. Samples were prepared for analysis by acetonitrile (22.0 microg/mL) plasma protein precipitation with droperidol as an internal standard, followed by a double-step liquid-liquid extraction with hexane : chloroform (70:30) prior to C-18 separation. Isocratic elution was achieved using a 0.1% (v/v) trifluoroacetic acid in deionized water, methanol and acetonitrile (45/27.5/27.5, v/v/v). Triple-wavelength diode-array detection at the lambda(max) of 245 nm for haloperidol, 254 nm for the diazepane analog and droperidol, and 240 nm for bromocriptine was carried out. The LLOQ of DAL, HAL, and BCT were 45.0, 56.1, and 150 ng/mL, respectively. In rats, the estimated pharmacokinetic parameters (i.e., t(1/2), CL, and V(ss)) of HAL when administered with DAL and BCT were t(1/2) = 16.4 min, V(ss) = 0.541 L/kg for HAL, t(1/2) = 28.0 min, V(ss) = 2.00 L/kg for DAL, and t(1/2) = 24.0 min, V(ss) = 0.106 L/kg for BCT. The PK parameters for HAL differed significantly from those previously reported, which may be an indication of a drug-drug interaction.

Simultaneous analysis of haloperidol, its three metabolites and two other butyrophenone-type neuroleptics by high performance liquid chromatography with dual ultraviolet detection.

We investigated simultaneous determination of haloperidol (HAL), its three metabolites [reduced HAL (R-HAL), 3-(4-fluorobenzoyl)propionic acid (FBPA) and 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP)] and two related compounds [spiperone (SPI) and droperidol (DRO)] in phosphate-buffered saline using high-performance liquid chromatography (HPLC) coupled with dual ultraviolet detection (220 and 250 nm). Retention times of HAL, R-HAL, FBPA, CPHP, SPI and DRO were 16.8, 11.8, 10.2, 4.1, 12.6 and 8.3 min, respectively. Their lower limits of detection were 7.5, 14, 4.5, 12, 10 and 20 ng/mL in the same order. The coefficients of variation for their intra- and inter-day assays were less than 7.8 and 9.4%, respectively. Of the other centrally acting drugs, only amoxapine interfered with the peak of DRO. Using our procedure, the binding study of tested compounds to synthetic melanin, human serum albumin and alpha1-acid glycoprotein was performed by determining the unbound concentration to total concentration ratio. These results indicated that simultaneous assay of HAL, R-HAL, FBPA, CPHP, SPI and DRO in phosphate-buffered saline by HPLC equipped with dual ultraviolet detection is simple, sensitive and reproducible. Also, our assay system can be applied to the binding study of these compounds to synthetic melanin, human serum albumin and alpha1-acid glycoprotein.

Derivative spectrophotometric determination of droperidol in presence of parabens.

We have developed a fast and accurate method for the determination of droperidol in the presence of methylparaben and propylparaben using derivative spectrophotometry. The first derivative amplitudes at 255.2 nm were selected for the assay. Calibration graph follows Beer's law in the range of 5-35 microg ml(-1). The coefficient of variation (CV) for intra-day and inter-day precision were less than 1.0 and 2.0%, respectively. The method was applied in the quality control of commercial oral and injection solutions and proved to be suitable for routine analysis.

LC determination and degradation study of droperidol.

A specific, high performance liquid chromatographic method for the determination of droperidol in the presence of its degradation products is described. The method is based on the use of an amide functionalized bonded phase column (LC-ABZ(+) Plus) and a simple mobile phase of methanol-sodium phosphate monobasic (0.05 M, pH 4.5) (40:60, v/v). It enables the resolution of eight compounds from the parent drug and from each other. The degradation was carried out in hydrochloric acid, sodium hydroxide and hydrogen peroxide. The main degradation products were identified. Application of the assay for a commercial preparation of droperidol for injection is presented.

Voltammetric determination of droperidol and benperidol.

In this study two butyrophenones, droperidol and benperidol were voltammetrically investigated using platinum and specially activated glass carbon electrodes. The behaviours of the substance were investigated in various electrolyte solutions having different pH values and by different scan rates. As a result of the studies it was shown that the quantitative determinations of the substances from their pharmaceutical preparations could be made rapidly and simply without any separation from the excipients.