Determination of oxytocin in a dilute IV solution by LC-MS(n).
The most common drug prescribed to induce labor in the United States is oxytocin, a peptide hormone composed of nine amino acids. Oxytocin is often reconstituted in intravenous (IV) saline solutions at less than 0.05 units ml(-1) (125 ng ml(-1)) to be delivered at 1-4 drops per minute. Existing LC-UV methods for oxytocin do not have sufficient detection limits to quantitate and/or confirm oxytocin in IV solutions without sample concentration. A determinative and confirmatory method for oxytocin was developed using an LC-MS(n) ion trap instrument with an electrospray ionization (ESI) interface in positive ion mode. Separation was achieved on a C-18 column using an isocratic elution of water with 50% acetonitrile (v/v) and water with 0.05% formic acid (v/v) at a flow rate of 250 microl min(-1). Data was acquired from the selected ion monitoring (SIM) of the precursor ion (m/z 1007.3) and MS(2) scans from the collision induced dissociation of m/z 1007.3 at 30% collision energy. In this method, MS(2) full scans were utilized to obtain three structurally significant ions for the unambiguous identification of oxytocin. Calibration standards, prepared in de-ionized water from 0.006 to 0.046 units ml(-1), were linear with an R(2) value of 0.9983. The methods LOD and LOQ were 0.00084 and 0.0029 units ml(-1) (2 and 7 ng ml(-1)), respectively. This LC-MS(n) method was used to determine the amount of oxytocin in a 0.04 units ml(-1) clinical sample that was prepared in 0.9% sodium chloride IV solution.
Karbiwnyk
Christine M
CM
Animal Drugs Research Center, Food and Drug Administration, Denver, CO 80225-0087, United States. christine.karbiwnyk@fda.hhs.gov
Faul
Kent C
KC
Turnipseed
Sherri B
SB
Andersen
Wendy C
WC
Miller
Keith E
KE
D055598:Chemical Phenomena; D002853:Chromatography, Liquid / Q000379:methods*; D006728:Hormones / Q000032:analysis* / Q000737:chemistry; D007262:Infusions, Intravenous; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D010121:Oxytocin / Q000032:analysis* / Q000737:chemistry; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012996:Solutions / Q000737:chemistry*
D006728:Hormones; D012996:Solutions; D010121:Oxytocin