Development of LC-MS/MS method for the determination of dapiprazole on dried blood spots and urine: application to pharmacokinetics.
A rapid and highly sensitive liquid chromatography–tandem mass spectrometric (LC-MS/MS) method for determination of dapiprazole on rat dried blood spots and urine was developed and validated. The chromatographic separation was achieved on a reverse-phase C18 column (250 × 4.6 mm i.d., 5 µm), using 20 mm ammonium acetate (pH adjusted to 4.0 with acetic acid) and acetonitrile (80:20, v/v) as a mobile phase at 25 °C. LC-MS detection was performed with selective ion monitoring using target ions at m/z 326 and m/z 306 for dapiprazole and mepiprazole used as internal standard, respectively. The calibration curve showed a good linearity in the concentration range of 1–3000 ng/mL. The effect of hematocrit on extraction of dapiprazole from DBS was evaluated. The mean recoveries of dapiprazole from DBS and urine were 93.88 and 90.29% respectively. The intra- and inter-day precisions were <4.19% in DBS as well as urine. The limits of detection and quantification were 0.30 and 1.10 ng/mL in DBS and 0.45 and 1.50 ng/mL in urine samples, respectively. The method was validated as per US Food and Drug Administration guidelines and successfully applied to a pharmacokinetic study of dapiprazole in rats.
Thippani
T
Ramesh
Pothuraju Nageswara
PN
Rao
Ramisetti Nageswara
RN
Rao
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D008297:Male; D010879:Piperazines / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014230:Triazoles / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*
D010879:Piperazines; D014230:Triazoles; C035289:dapiprazole