Positive mode electrospray ionization mass spectrometry of bisphosphonates using dicationic and tricationic ion-pairing agents.
A general method for detecting bisphosphonate drugs by ESI-MS and LC-ESI-MS as positive ions has been developed. Bisphosphonates can have multiple negative charges in solution. Tricationic ion-pairing reagents were paired with bisphosphonates to form a positively charged complex. It was clear that this facile pairing method worked. However, an appreciable presence of -1 bisphosphonate species were observed in positive mode ESI-MS (i.e. as the +2 complex with tricationic reagents). This led to an extended investigation on the use of dicationic pairing agents. The use of dicationic reagents improved the detection sensitivity for all of the bisphosphonates. Tandem mass spectrometry also improved the limits of detection for most of the bisphosphonates using both the tricationic and dicationic pairing reagents. A tricationic reagent also was used as an ion-pairing reagent in chromatography experiments. Thus the addition of a single reagent produced benefits in that it increased chromatographic retention and enhanced the ESI-MS detection of bisphosphonates.
Warnke
Molly M
MM
Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington, TX 76019, USA.
Breitbach
Zachary S
ZS
Dodbiba
Edra
E
Crank
Jeffrey A
JA
Payagala
Tharanga
T
Sharma
Pritesh
P
Wanigasekara
Eranda
E
Zhang
Xiaotong
X
Armstrong
Daniel W
DW
D002412:Cations / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004164:Diphosphonates / Q000032:analysis*; D015394:Molecular Structure; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry
D002412:Cations; D004164:Diphosphonates