Determination of paroxetine in human saliva by reversed-phase high-performance liquid chromatography with UV detection.

A rapid and sensitive high-performance liquid chromatographic method was validated and described for determination of paroxetine in human saliva. Following liquid-liquid extraction of the drug and an internal standard (dibucaine), chromatographic separation was accomplished using a C18 analytical column with a mobile phase consisting of 0.05 mol/L sodium phosphate buffer, pH 5.0, and acetonitrile (A 30:70, v/v; B 60:40, v/v). Paroxetine and the internal standard were detected by ultraviolet absorbance at 205 nm. The average recoveries of the drug and internal standard were 92.5% and 89%, respectively. The lower limits of detection and quantification were 1 and 4 ng/ml, respectively, and the calibration curve was linear over a concentration range of 4 ng/ml. The saliva level of paroxetine in patients with depression taking 10 to 40 mg/day of the drug was significantly correlated with the plasma level of paroxetine in each patient (r = 0.617, P < 0.004, n = 19). These data indicate that the saliva level of paroxetine could be a useful marker to predict the plasma level of the drug.

A case of severe parkinsonism associated with short-term treatment with milnacipran.

A 51-year-old woman became depressed following the death of her father-in-law. She was given 50 mg of milnacipran a day. One week after starting milnacipran, she developed parkinsonism. The milnacipran was increased to 100 mg/d, resulting in a situation where her symptoms of parkinsonism and depression worsened, which was associated with the reduction of 125I-meta-iodobenzylguanidine (MIBG) uptake. Three hundred milligrams of levodopa plus 30 mg of carbidopa was subsequently added to her medications. However, her symptoms still continued for 2 more weeks. Then the milnacipran was tapered, and she was given fluvoxamine with levodopa plus carbidopa. The parkinsonism and the depression gradually improved within 1 month after starting the regimen of fluvoxamine. The MIBG uptake also recovered (Heart to Lung ratio, 2.1) within 2 months. To our knowledge, this is the second reported case of parkinsonism associated with the use of serotonin noradrenaline reuptake inhibitor. This case showed a transient reduction of MIBG uptake associated with the parkinsonism and depression. Clinicians should be aware that serotonin noradrenaline reuptake inhibitors as well as selective serotonin reuptake inhibitors can cause parkinsonism.