A high-performance liquid chromatographic-atmospheric pressure chemical ionization-tandem mass spectrometric method for determination of risperidone and 9-hydroxyrisperidone in human plasma.
Risperidone, a benzisoxazole derivative, is an antipsychotic agent used for the treatment of schizophrenia. We developed a liquid chromatographic-atmospheric pressure chemical ionization-tandem mass spectrometric (LC-APCI-MS-MS) method with improved sensitivity, selectivity, and dynamic range for determination of risperidone and 9-hydroxyrisperidone in human plasma. A structural analogue of risperidone, RO68808 (5 ng/mL), is added as the internal standard to 1 mL of human plasma. Plasma is made basic, extracted with pentane/methylene chloride (3:1), the organic phase evaporated to dryness, and the residue is reconstituted in water with 0.1% formic acid/acetonitrile (20:1). For LC-MS-MS analysis, a Metachem Inertsel HPLC column (2.1 x 150 mm, 5-microm particle size) is connected to a Finnigan TSQ7000 tandem MS via the Finnigan API interface. Both electrospray (ESI) and APCI produced predominantly MH(+) ions for the two analytes and the internal standard. Ions detected by selected reaction monitoring correspond to the following transitions: m/z 411 to 191 for risperidone, m/z 427 to 207 for 9-hydroxyrisperidone, and m/z 421 to 201 for the internal standard. APCI provided a larger dynamic range (0.1 to 25 ng/mL) and better precision and accuracy than ESI. Intrarun accuracy and precision determined at 0.1, 0.25, 2.5, and 15 ng/mL were within 12% of target with %CVs not exceeding 10.9%. Interrun accuracy and precision determined at the same concentrations were within 9.6% of target with %CVs not exceeding 6.7%. Analytes were stable in plasma after 24 h at room temperature, 2 freeze-thaw cycles, and 490 days at -20 degrees C.
Moody
David E
DE
Center for Human Toxicology, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, USA. dmoody@alanine.pharm.utah.edu
Laycock
John D
JD
Huang
Wei
W
Foltz
Rodger L
RL
D014150:Antipsychotic Agents / Q000097:blood*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D006801:Humans; D007202:Indicators and Reagents; D007555:Isoxazoles / Q000097:blood*; D013058:Mass Spectrometry; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000097:blood*; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D018967:Risperidone / Q000097:blood*
D014150:Antipsychotic Agents; D007202:Indicators and Reagents; D007555:Isoxazoles; D011743:Pyrimidines; D018967:Risperidone; D000068882:Paliperidone Palmitate