Fragmentation pathways of eight nitrogen-containing bisphosphonates (BPs) investigated by ESI-MSn in negative ion mode

An innovative derivatization‐free IC‐MS/MS method for the detection of bisphosphonates in horse plasma

“…In addition, all the bisphosphonic acids presented the same neutral loss H 3 PO 3 (82 Da). The proposed fragmentation pathways have already been described by Hardouin et al 32 for alendronic acid, by Qu et al 33 for alendronic acid, pamidronic acid, and risedronic acid and by Popot et al 7 for clodronic acid and tiludronic acid. Furthermore, a successive loss of H 3 PO 3 and H 2 O is generated from nitrogen‐containing bisphosphonates which bear a hydroxide chemical function on the carbon atom linked to phosphonate groups.…”

Synthesis of Hydroxymethylenebisphosphonic Acid Derivatives in Different Solvents

“…Reacting β-alanine with an unnecessarily large amount of phosphorus trichloride (5 equivalents) and phosphorous acid (3 equivalents) under MW conditions, sodium pamidronate was isolated in a yield of 67% (Table 15/Entry 1) [51]. A rather similar yield (61%) was reported applying the above P-reagents in a 2:1.5 equivalents quantity (Table 15/Entry 2) [52]. Keglevich et al obtained pure pamidronic acid in a yield of 44%, when both phosphorus trichloride and phosphorous acid were used in a quantity of 2 equivalents [53].…”

“…Alendronic acid derivatives were prepared starting from GABA, N -phthalimido-GABA, or N -phthalimido-GABA-chloride, but the purities were not reported at all. Using GABA as the starting material, and phosphorus trichloride along with Ms 2 O or phosphorous acid as the other reagent in a molar ratio of 3:3 (PCl 3 :Ms 2 O) and 5:3 (PCl 3 :H 3 PO 3 under MW conditions), or 2:1.5 (PCl 3 :H 3 PO 3 ), the yields were 78%, 78% and 59%, respectively (Table 16/Entries 1–3) [48,51,52]. Starting from N -phthalimido-GABA and applying phosphorus trichloride along with phosphorous acid, or this combined with phosphoric acid, crude alendronic acid was obtained in yields of 38% and 57% (Table 16/Entries 4–5) [54].…”

“…Yields around 66% were claimed using ca. 2 equivalents of both phosphorus trichloride and phosphorous acid at a temperature of 70–100 °C (Table 18/Entries 3 and 4) [52,61]. Carrying out the reaction applying 3.2 equivalents of phosphoryl chloride and a large excess (9.7 equivalents) of phosphorous acid, the yield was 60% (Table 18/Entry 5) [59].…”

H2O loss in the fragmentation of deprotonated N‐o‐tolylamides in tandem mass spectrometry

“…Loss of water is common in the fragmentation of protonated molecules, such as carboxylic acids, aldehydes, esters, alcohols, amides [22][23][24][25][26][27] and deprotonated molecules which contain hydroxyl groups. [28][29][30] However, loss of water has been rarely reported in the fragmentation of deprotonated amides. [15] In order to gain insight into the mechanism of H 2 O loss, the fragmentations of deprotonated ions of a series of N-o-tolylamides were also studied ( Table 1).…”