title: Simultaneous determination of etoposide and a piperine analogue (PA-1) by UPLC-qTOF-MS: evidence that PA-1 enhances the oral bioavailability of etoposide in mice.
abstract: In the present investigation, a UPLC-qTOF-MS/MS method has been developed for the simultaneous determination of etoposide and a piperine analogue, namely, 4-ethyl 5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienoic acid piperidide (PA-1). The analytes were separated on a reverse phase C18 column using methanol-water (72:28, v/v) mobile phase with a flow rate of 250 microL/min. The qTOF-MS was operated under multiple reaction monitoring mode using electro-spray ionization (ESI) technique with positive ion polarity. The major product ions for etoposide and PA-1 were at m/z 185.1350 and 164.1581, respectively. The recovery of the analytes from mouse plasma was optimized using solid phase extraction technique. The total run time was 6 min and the elution of etoposide and PA-1 occurred at 1.24 and 2.84 min, respectively. The calibration curves of etoposide as well as PA-1 were linear over the concentration range of 2-1000 ng/mL (r(2), 0.9829), and 1-1000 ng/mL (r(2), 0.9989), respectively. For etoposide intra-assay and inter-assay accuracy in terms of % bias was in between -7.65 to +6.26, and -7.83 to +5.99, respectively. For PA-1 intra-assay and inter-assay accuracy in terms of % bias was in between -7.01 to +9.10, and -7.36 to +6.71, respectively. The lower limit of quantitation for etoposide and PA-1 were 2.0 and 1.0 ng/mL, respectively. Analytes were stable under various conditions (in autosampler, during freeze-thaw, at room temperature, and under deep-freeze conditions). The method was used for a pharmacokinetic study which showed that PA-1 enhanced the oral bioavailability of etoposide in mice by 2.32-fold.
authors.affiliation: PK/PD and Toxicology Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India.
authors.forename: B S
authors.initials: BS
authors.lastname: Sachin
authors.forename: I A
authors.initials: IA
authors.lastname: Najar
authors.forename: S C
authors.initials: SC
authors.lastname: Sharma
authors.forename: M K
authors.initials: MK
authors.lastname: Verma
authors.forename: M V
authors.initials: MV
authors.lastname: Reddy
authors.forename: R
authors.initials: R
authors.lastname: Anand
authors.forename: R K
authors.initials: RK
authors.lastname: Khajuria
authors.forename: S
authors.initials: S
authors.lastname: Koul
authors.forename: R K
authors.initials: RK
authors.lastname: Johri
mesh_terms: D000470:Alkaloids / Q000097:blood* / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood* / Q000493:pharmacokinetics; D052117:Benzodioxoles / Q000097:blood* / Q000138:chemical synthesis / Q000737:chemistry*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004337:Drug Carriers / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry; D005047:Etoposide / Q000097:blood* / Q000493:pharmacokinetics; D051379:Mice; D010880:Piperidines / Q000097:blood* / Q000138:chemical synthesis / Q000737:chemistry*; D053284:Polyunsaturated Alkamides / Q000097:blood* / Q000138:chemical synthesis / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D052117:Benzodioxoles; D004337:Drug Carriers; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D005047:Etoposide; C008922:piperine