Simultaneous detection of cisatracurium, its degradation products and propofol using positive ion detection followed by negative ion detection in a single LC/MS run

Wang, P; Zhang, H; Stewart, James T.; Bartlett, Michael G.

doi:10.1016/s0731-7085(97)00222-7

Cited by 10 publications

(3 citation statements)

References 30 publications

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“…Not only are these compounds potentially subject to the actions of endogenous esterase enzymes, but they are also inherently chemically unstable, readily undergoing hydrolysis (especially under basic conditions) to yield quaternary alcoholic and quaternary acidic breakdown products. Atracurium also undergoes chemical degradation to yield the alkaloid laudanosine and a quaternary monoacrylate as breakdown products [15,16]. The instability of these four drugs is such that the parent compounds often do not survive the analytical process, even with spiked specimens; this is especially true for atracurium and mivacurium.…”

Section: Resultsmentioning

confidence: 99%

An analytical strategy for quaternary ammonium neuromuscular blocking agents in a forensic setting using LC-MS/MS on a tandem quadrupole/time-of-flight instrument

Ballard¹,

Vickery²,

Nguyễn³

et al. 2006

J. Am. Soc. Mass Spectrom.

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An analytical strategy is described for analyzing quaternary ammonium neuromuscular blocking agents in a wide variety of biological specimens in a forensic setting. Neuromuscular blocking agents such as succinylcholine, pancuronium, and tubocurarine, often used as paralytic agents during surgery, are occasionally suspected as paralytic poisoning agents involved in suspected homicide and suicide cases. Because suspicion in such cases can develop slowly, the age, nature, and quality of available specimens varies greatly. The compounds are challenging analytically because of their simultaneous precharged yet lipophilic character. An analytical strategy has been devised for extracting these compounds from complex matrices using a combination of a modified Bligh and Dyer liquid-liquid extraction (used in reverse) followed by reverse-phase ion pairing solid-phase extraction using heptafluorobutyric acid as an ion pairing reagent. Final analysis is by LC-MS/MS using a tandem quadrupole orthogonal acceleration time of flight instrument (Q-TOF) with repetitive product ion scanning at high resolution. Native and spiked specimens are compared for both quantitative and especially qualitative purposes. The method has been applied to a wide variety of fluid and tissue specimen types, including numerous specimens from exhumation autopsies. For most specimens, detection limits are in the 2 to 10 ng/g range. Succinylmonocholine has been demonstrated to be present at low levels in normal posthumous kidney and liver. The Q-TOF is an excellent platform for forensic analytical investigations. This analytical strategy should also be applicable to other problematic analytes and sample matrices. (J Am Soc Mass

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Section: Resultsmentioning

confidence: 99%

An analytical strategy for quaternary ammonium neuromuscular blocking agents in a forensic setting using LC-MS/MS on a tandem quadrupole/time-of-flight instrument

Ballard¹,

Vickery²,

Nguyễn³

et al. 2006

J. Am. Soc. Mass Spectrom.

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“…One report on the fragmentation of phenolic anions in the gas phase is restricted to phenol only [12]. Reports on negative ion LC/MS for the identification of propofol using APCI for ionization fail to discuss its fragmentation [15,16]. Fragmentation of the [M ϩ H] ϩ ion of sterically hindered phenols formed by chemical ionization using methane or butane as the reagent gas [17,18] indicate the formation of product ions by the loss of a methyl radical at the ␤ carbon of substituent side chains.…”

Section: The Presence Of the Intermediary [M ϫ H ϫ Ch 3 ]mentioning

confidence: 99%

Mass spectral fragmentation of the intravenous anesthetic propofol and structurally related phenols

Bajpai

Varshney

Seubert

et al. 2005

J. Am. Soc. Mass Spectrom.

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Propofol (2,6-diisopropyl phenol) is a widely used intravenous anesthetic. To define its pharmacokinetics and pharmacodynamics, methods for its quantitation in biological matrixes have been developed, but its pattern of mass spectral fragmentation is unknown. We found that fragmentation of the [M Ϫ H] Ϫ ion (m/z 177) of propofol in both APCI MS/MS and ESI MS/MS involves the stepwise loss of a methyl radical and a hydrogen radical from one isopropyl side chain to give the most intense product ion, [M ϪH Ϫ CH 4 ] Ϫ , at m/z 161. This two-step process is also the preferred mode of fragmentation for similar branched alkyl substituted phenols. This mode of fragmentation of the [M Ϫ H] Ϫ ion is supported by three independent lines of evidence: (1) Ϫ product ion. Phenols with a single straight chain alkyl substituent, in contrast, undergo ␤ elimination of the alkyl radical irrespective of the length of the alkyl chain, yielding the most intense product ion at m/z 106. This product ion represents a special case of a stable intermediary radical for the two-step process described for branched side chains, because further elimination of a hydrogen radical from the ␤ carbon is not possible. as a supplement to regional anesthesia and in critically ill patients confined to intensive care units. The patient loses consciousness 30 to 50 s after receiving the drug and remains asleep for about 4 to 6 min [1,2]. Even though a single dose of propofol has a short duration of action and produces fast recovery from anesthesia, propofol is not metabolized in a few minutes. It is present in blood, adipose tissues, liver, and brain for a few hours, its concentration decreasing with time [4].

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“…ESI has good ion current stability, which when coupled to the lower applied accelerating voltages in the quadrupole mass spectrometer makes it possible to monitor both positive and negative ions in the same LC-MS-MS run. The instrument used by Wang et al switched between ion polarities every 0.05 s while maintaining a stable baseline (Wang et al, 1998). The positive ion ESI mode was selected for 3TC and d4T because of improved sensitivity due to the presence of amino groups, which are easily protonated under the acidic mobile phase conditions (pH 4.5).…”

Section: Introductionmentioning

confidence: 99%

Determination of lamivudine/stavudine/efavirenz in human serum using liquid chromatography/electrospray tandem mass spectrometry with ionization polarity switch

Fan

Bartlett

Stewart

2002

Biomedical Chromatography

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A high-performance liquid chromatography/tandem mass spectrometry (LC-MS-MS) method with ionization polarity switch was developed and validated in human serum for the determination of a lamivudine (3TC)/stavudine (d4T)/efavirenz combination HIV therapy. Solid phase extraction (SPE) was used to extract these anti-HIV drugs and internal standard aprobarbital. A gradient mobile phase consisting of acetonitrile and 20 mM ammonium acetate buffer with pH adjusted to 4.5 using glacial acetic acid was utilized to separate these drugs on a hexylsilane column (150 x 2.0 mm i.d.). The total run time between injections was 18 min. The precursor and major product ions of these drugs were monitored on a triple quadrupole mass spectrometer in the multiple reactions monitoring (MRM) mode. Ionization polarity was switched in the middle of the LC run allowing these anti-HIV drugs with different physicochemical properties to be detected simultaneously. The effect of ion suppression from human serum was studied and no interference with the analysis was noted. The method was validated over the range of 1.1-540 ng/mL for 3TC, 12.5-6228 ng/mL for d4T and 1.0-519 ng/mL for efavirenz. The method was shown to be accurate, with intra-day and inter-day accuracy less than 14.0% and precise, with intra-day and inter-day precision less than 13.1%. The extraction recoveries of all analytes were higher than 90%.

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Simultaneous detection of cisatracurium, its degradation products and propofol using positive ion detection followed by negative ion detection in a single LC/MS run

Cited by 10 publications

References 30 publications

An analytical strategy for quaternary ammonium neuromuscular blocking agents in a forensic setting using LC-MS/MS on a tandem quadrupole/time-of-flight instrument

An analytical strategy for quaternary ammonium neuromuscular blocking agents in a forensic setting using LC-MS/MS on a tandem quadrupole/time-of-flight instrument

Mass spectral fragmentation of the intravenous anesthetic propofol and structurally related phenols

Determination of lamivudine/stavudine/efavirenz in human serum using liquid chromatography/electrospray tandem mass spectrometry with ionization polarity switch

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